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Blood Monocytes and Their Subsets in Health and Disease

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Macrophages: Biology and Role in the Pathology of Diseases

Abstract

Monocytes are blood leukocytes, which derive from bone marrow and can go into tissue where they develop into macrophages. By standard morphology monocytes are hard to define but with determination of cell surface markers in flow cytometry they can be clearly identified. They are versatile cells that can perform phagocytosis, cytokine production, and antigen presentation. Blood monocytes can be subdivided into classical, intermediate, and non-classical cells and these subsets are functionally distinct. The monocyte subsets respond with changes in number and function to various inflammatory and malignant diseases. Given their role in disease therapeutic strategies to target monocytes and their subsets are being explored. In animal models blood monocytes show similar subsets and functional properties but there are also important differences, which preclude a direct transfer of animal data to man.

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References

  • Abeles RD, McPhail MJ, Sowter D, Antoniades CG, Vergis N, Vijay GK, Xystrakis E, Khamri W, Shawcross DL, Ma Y, Wendon JA, Vergani D (2012) CD14, CD16 and HLA-DR reliably identifies human monocytes and their subsets in the context of pathologically reduced HLA-DR expression by CD14(hi)/CD16(neg) monocytes: expansion of CD14(hi)/CD16(pos) and contraction of CD14(lo)/CD16(pos) monocytes in acute liver failure. Cytometry A 81(10):823–834. doi:10.1002/cyto.a.22104

    PubMed  Google Scholar 

  • Ahuja V, Miller SE, Howell DN (1995) Identification of two subpopulations of rat monocytes expressing disparate molecular forms and quantities of CD43. Cell Immunol 163(1):59–69. doi:10.1006/cimm.1995.1099

    CAS  PubMed  Google Scholar 

  • Alder JK, Georgantas RW 3rd, Hildreth RL, Kaplan IM, Morisot S, Yu X, McDevitt M, Civin CI (2008) Kruppel-like factor 4 is essential for inflammatory monocyte differentiation in vivo. J Immunol 180(8):5645–5652

    CAS  PubMed Central  PubMed  Google Scholar 

  • Allen JB, Wong HL, Guyre PM, Simon GL, Wahl SM (1991) Association of circulating receptor Fc gamma RIII-positive monocytes in AIDS patients with elevated levels of transforming growth factor-beta. J Clin Invest 87(5):1773–1779. doi:10.1172/JCI115196

    CAS  PubMed Central  PubMed  Google Scholar 

  • Amoras AL, da Silva MT, Zollner RL, Kanegane H, Miyawaki T, Vilela MM (2007) Expression of Fc gamma and complement receptors in monocytes of X-linked agammaglobulinaemia and common variable immunodeficiency patients. Clin Exp Immunol 150(3):422–428. doi:10.1111/j.1365-2249.2007.03512.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ancuta P, Rao R, Moses A, Mehle A, Shaw SK, Luscinskas FW, Gabuzda D (2003) Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med 197(12):1701–1707. doi:10.1084/jem.20022156

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ancuta P, Autissier P, Wurcel A, Zaman T, Stone D, Gabuzda D (2006) CD16+ monocyte-derived macrophages activate resting T cells for HIV infection by producing CCR3 and CCR4 ligands. J Immunol 176(10):5760–5771

    CAS  PubMed  Google Scholar 

  • Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, Zaman T, Stone D, Mefford M, Morgello S, Singer EJ, Wolinsky SM, Gabuzda D (2008) Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One 3(6):e2516. doi:10.1371/journal.pone.0002516

    PubMed Central  PubMed  Google Scholar 

  • Antoniades CG, Berry PA, Davies ET, Hussain M, Bernal W, Vergani D, Wendon J (2006) Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure. Hepatology 44(1):34–43. doi:10.1002/hep.21240

    CAS  PubMed  Google Scholar 

  • Aspinall AI, Curbishley SM, Lalor PF, Weston CJ, Miroslava B, Liaskou E, Adams RM, Holt AP, Adams DH (2010) CX(3)CR1 and vascular adhesion protein-1-dependent recruitment of CD16(+) monocytes across human liver sinusoidal endothelium. Hepatology 51(6):2030–2039. doi:10.1002/hep.23591

    PubMed Central  PubMed  Google Scholar 

  • Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, Sarnacki S, Cumano A, Lauvau G, Geissmann F (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317(5838):666–670. doi:10.1126/science.1142883

    CAS  PubMed  Google Scholar 

  • Azeredo EL, Neves-Souza PC, Alvarenga AR, Reis SR, Torrentes-Carvalho A, Zagne SM, Nogueira RM, Oliveira-Pinto LM, Kubelka CF (2010) Differential regulation of toll-like receptor-2, toll-like receptor-4, CD16 and human leucocyte antigen-DR on peripheral blood monocytes during mild and severe dengue fever. Immunology 130(2):202–216. doi:10.1111/j.1365-2567.2009.03224.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baeten D, Boots AM, Steenbakkers PG, Elewaut D, Bos E, Verheijden GF, Berheijden G, Miltenburg AM, Rijnders AW, Veys EM, De Keyser F (2000) Human cartilage gp-39+, CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis. Arthritis Rheum 43(6):1233–1243. doi:10.1002/1529-0131(200006)43:6<1233::AID-ANR6>3.0.CO;2-9

    CAS  PubMed  Google Scholar 

  • Baj-Krzyworzeka M, Baran J, Weglarczyk K, Szatanek R, Szaflarska A, Siedlar M, Zembala M (2010) Tumour-derived microvesicles (TMV) mimic the effect of tumour cells on monocyte subpopulations. Anticancer Res 30(9):3515–3519

    PubMed  Google Scholar 

  • Balboa L, Romero MM, Laborde E, Sabio YGCA, Basile JI, Schierloh P, Yokobori N, Musella RM, Castagnino J, de la Barrera S, Sasiain MC, Aleman M (2013) Impaired dendritic cell differentiation of CD16-positive monocytes in tuberculosis: role of p38 MAPK. Eur J Immunol 43(2):335–347. doi:10.1002/eji.201242557

    CAS  PubMed  Google Scholar 

  • Barbosa RR, Silva SP, Silva SL, Tendeiro R, Melo AC, Pedro E, Barbosa MP, Santos MC, Victorino RM, Sousa AE (2012) Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels. Clin Exp Immunol 169(3):263–272. doi:10.1111/j.1365-2249.2012.04620.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, Espevik T, Ziegler-Heitbrock L (2002) The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol 168(7):3536–3542

    CAS  PubMed  Google Scholar 

  • Bergmann CE, Hoefer IE, Meder B, Roth H, van Royen N, Breit SM, Jost MM, Aharinejad S, Hartmann S, Buschmann IR (2006) Arteriogenesis depends on circulating monocytes and macrophage accumulation and is severely depressed in op/op mice. J Leukoc Biol 80(1):59–65. doi:10.1189/jlb.0206087

    CAS  PubMed  Google Scholar 

  • Biburger M, Aschermann S, Schwab I, Lux A, Albert H, Danzer H, Woigk M, Dudziak D, Nimmerjahn F (2011) Monocyte subsets responsible for immunoglobulin G-dependent effector functions in vivo. Immunity 35(6):932–944. doi:10.1016/j.immuni.2011.11.009

    CAS  PubMed  Google Scholar 

  • Bigley V, Haniffa M, Doulatov S, Wang XN, Dickinson R, McGovern N, Jardine L, Pagan S, Dimmick I, Chua I, Wallis J, Lordan J, Morgan C, Kumararatne DS, Doffinger R, van der Burg M, van Dongen J, Cant A, Dick JE, Hambleton S, Collin M (2011) The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J Exp Med 208(2):227–234. doi:10.1084/jem.20101459

    CAS  PubMed Central  PubMed  Google Scholar 

  • Blumenstein M, Boekstegers P, Fraunberger P, Andreesen R, Ziegler-Heitbrock HW, Fingerle-Rowson G (1997) Cytokine production precedes the expansion of CD14+CD16+ monocytes in human sepsis: a case report of a patient with self-induced septicemia. Shock 8(1):73–75

    CAS  PubMed  Google Scholar 

  • Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: a new hypothesis for pathogenesis of the disease process. Chest 112(1):235–243

    CAS  PubMed  Google Scholar 

  • Bruhl H, Cihak J, Plachy J, Kunz-Schughart L, Niedermeier M, Denzel A, Rodriguez Gomez M, Talke Y, Luckow B, Stangassinger M, Mack M (2007) Targeting of Gr-1+, CCR2+ monocytes in collagen-induced arthritis. Arthritis Rheum 56(9):2975–2985. doi:10.1002/art.22854

    PubMed  Google Scholar 

  • Burke B, Ahmad R, Staples KJ, Snowden R, Kadioglu A, Frankenberger M, Hume DA, Ziegler-Heitbrock L (2008) Increased TNF expression in CD43++ murine blood monocytes. Immunol Lett 118(2):142–147. doi:10.1016/j.imlet.2008.03.012

    CAS  PubMed  Google Scholar 

  • Cairns AP, Crockard AD, Bell AL (2002) The CD14+ CD16+ monocyte subset in rheumatoid arthritis and systemic lupus erythematosus. Rheumatol Int 21(5):189–192

    PubMed  Google Scholar 

  • Centlivre M, Legrand N, Steingrover R, van der Sluis R, Grijsen ML, Bakker M, Jurriaans S, Berkhout B, Paxton WA, Prins JM, Pollakis G (2011) Altered dynamics and differential infection profiles of lymphoid and myeloid cell subsets during acute and chronic HIV-1 infection. J Leukoc Biol 89(5):785–795. doi:10.1189/jlb.0410231

    CAS  PubMed  Google Scholar 

  • Chao LC, Soto E, Hong C, Ito A, Pei L, Chawla A, Conneely OM, Tangirala RK, Evans RM, Tontonoz P (2013) Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice. J Lipid Res 54(3):806–815. doi:10.1194/jlr.M034157

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clemens DL, Lee BY, Horwitz MA (2012) O-antigen-deficient Francisella tularensis live vaccine strain mutants are ingested via an aberrant form of looping phagocytosis and show altered kinetics of intracellular trafficking in human macrophages. Infect Immun 80(3):952–967. doi:10.1128/IAI.05221-11

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cochain C, Rodero MP, Vilar J, Recalde A, Richart AL, Loinard C, Zouggari Y, Guerin C, Duriez M, Combadiere B, Poupel L, Levy BI, Mallat Z, Combadiere C, Silvestre JS (2010) Regulation of monocyte subset systemic levels by distinct chemokine receptors controls post-ischaemic neovascularization. Cardiovasc Res 88(1):186–195. doi:10.1093/cvr/cvq153

    CAS  PubMed  Google Scholar 

  • Combadiere C, Ahuja SK, Murphy PM (1995) Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene. DNA Cell Biol 14(8):673–680

    CAS  PubMed  Google Scholar 

  • Combadiere C, Potteaux S, Rodero M, Simon T, Pezard A, Esposito B, Merval R, Proudfoot A, Tedgui A, Mallat Z (2008) Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 117(13):1649–1657. doi:10.1161/CIRCULATIONAHA.107.745091

    CAS  PubMed  Google Scholar 

  • Coquillard G, Patterson BK (2009) Determination of hepatitis C virus-infected, monocyte lineage reservoirs in individuals with or without HIV coinfection. J Infect Dis 200(6):947–954. doi:10.1086/605476

    PubMed  Google Scholar 

  • Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, Puel A, Biswas SK, Moshous D, Picard C, Jais JP, D’Cruz D, Casanova JL, Trouillet C, Geissmann F (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33(3):375–386. doi:10.1016/j.immuni.2010.08.012

    CAS  PubMed Central  PubMed  Google Scholar 

  • Davies LC, Rosas M, Jenkins SJ, Liao CT, Scurr MJ, Brombacher F, Fraser DJ, Allen JE, Jones SA, Taylor PR (2013) Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation. Nat Commun 4:1886. doi:10.1038/ncomms2877

    PubMed  Google Scholar 

  • Dayyani F, Belge KU, Frankenberger M, Mack M, Berki T, Ziegler-Heitbrock L (2003) Mechanism of glucocorticoid-induced depletion of human CD14+CD16+ monocytes. J Leukoc Biol 74(1):33–39

    CAS  PubMed  Google Scholar 

  • Dayyani F, Joeinig A, Ziegler-Heitbrock L, Schmidmaier R, Straka C, Emmerich B, Meinhardt G (2004) Autologous stem-cell transplantation restores the functional properties of CD14+CD16+ monocytes in patients with myeloma and lymphoma. J Leukoc Biol 75(2):207–213. doi:10.1189/jlb.0803386

    CAS  PubMed  Google Scholar 

  • De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8(3):211–226. doi:10.1016/j.ccr.2005.08.002

    PubMed  Google Scholar 

  • Dimitrov S, Lange T, Born J (2010) Selective mobilization of cytotoxic leukocytes by epinephrine. J Immunol 184(1):503–511. doi:10.4049/jimmunol.0902189

    CAS  PubMed  Google Scholar 

  • Dimitrov S, Shaikh F, Pruitt C, Green M, Wilson K, Beg N, Hong S (2013) Differential TNF production by monocyte subsets under physical stress: blunted mobilization of proinflammatory monocytes in prehypertensive individuals. Brain Behav Immun 27(1):101–108. doi:10.1016/j.bbi.2012.10.003

    CAS  PubMed  Google Scholar 

  • Docke WD, Hoflich C, Davis KA, Rottgers K, Meisel C, Kiefer P, Weber SU, Hedwig-Geissing M, Kreuzfelder E, Tschentscher P, Nebe T, Engel A, Monneret G, Spittler A, Schmolke K, Reinke P, Volk HD, Kunz D (2005) Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study. Clin Chem 51(12):2341–2347. doi:10.1373/clinchem.2005.052639

    PubMed  Google Scholar 

  • Durbin AP, Vargas MJ, Wanionek K, Hammond SN, Gordon A, Rocha C, Balmaseda A, Harris E (2008) Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever. Virology 376(2):429–435. doi:10.1016/j.virol.2008.03.028

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fairbairn L, Kapetanovic R, Sester DP, Hume DA (2011) The mononuclear phagocyte system of the pig as a model for understanding human innate immunity and disease. J Leukoc Biol 89(6):855–871. doi:10.1189/jlb.1110607

    CAS  PubMed  Google Scholar 

  • Faivre S, Demetri G, Sargent W, Raymond E (2007) Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov 6(9):734–745. doi:10.1038/nrd2380

    CAS  PubMed  Google Scholar 

  • Fehlings MG, Nguyen DH (2010) Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury. J Clin Immunol 30(Suppl 1):S109–S112. doi:10.1007/s10875-010-9404-7

    CAS  PubMed  Google Scholar 

  • Feng AL, Zhu JK, Sun JT, Yang MX, Neckenig MR, Wang XW, Shao QQ, Song BF, Yang QF, Kong BH, Qu X (2011) CD16+ monocytes in breast cancer patients: expanded by monocyte chemoattractant protein-1 and may be useful for early diagnosis. Clin Exp Immunol 164(1):57–65. doi:10.1111/j.1365-2249.2011.04321.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fernandez GC, Ramos MV, Gomez SA, Dran GI, Exeni R, Alduncin M, Grimoldi I, Vallejo G, Elias-Costa C, Isturiz MA, Palermo MS (2005) Differential expression of function-related antigens on blood monocytes in children with hemolytic uremic syndrome. J Leukoc Biol 78(4):853–861. doi:10.1189/jlb.0505251

    CAS  PubMed  Google Scholar 

  • Fertl A, Menzel M, Hofer TP, Morresi-Hauf A, Ziegler-Heitbrock L, Frankenberger M (2008) Monitoring of glucocorticoid therapy by assessment of CD14(+)CD16(+) monocytes: a case report. Immunobiology 213(9–10):909–916. doi:10.1016/j.imbio.2008.07.018

    CAS  PubMed  Google Scholar 

  • Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ (2000) CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med 192(6):899–905

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fingerle G, Pforte A, Passlick B, Blumenstein M, Strobel M, Ziegler-Heitbrock HW (1993) The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients. Blood 82(10):3170–3176

    CAS  PubMed  Google Scholar 

  • Fingerle-Rowson G, Auers J, Kreuzer E, Fraunberger P, Blumenstein M, Ziegler-Heitbrock LH (1998a) Expansion of CD14+CD16+ monocytes in critically ill cardiac surgery patients. Inflammation 22(4):367–379

    CAS  PubMed  Google Scholar 

  • Fingerle-Rowson G, Angstwurm M, Andreesen R, Ziegler-Heitbrock HW (1998b) Selective depletion of CD14+ CD16+ monocytes by glucocorticoid therapy. Clin Exp Immunol 112(3):501–506

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frankenberger M, Hofer TP, Marei A, Dayyani F, Schewe S, Strasser C, Aldraihim A, Stanzel F, Lang R, Hoffmann R, Prazeres da Costa O, Buch T, Ziegler-Heitbrock L (2012) Transcript profiling of CD16-positive monocytes reveals a unique molecular fingerprint. Eur J Immunol 42(4):957–974. doi:10.1002/eji.201141907

    CAS  PubMed  Google Scholar 

  • Frankenberger M, Ekici AB, Angstwurm MW, Hoffmann H, Hofer TP, Heimbeck I, Meyer P, Lohse P, Wjst M, Haussinger K, Reis A, Ziegler-Heitbrock L (2013) A defect of CD16-positive monocytes can occur without disease. Immunobiology 218(2):169–174. doi:10.1016/j.imbio.2012.02.013

    CAS  PubMed  Google Scholar 

  • Frantz S, Hofmann U, Fraccarollo D, Schafer A, Kranepuhl S, Hagedorn I, Nieswandt B, Nahrendorf M, Wagner H, Bayer B, Pachel C, Schon MP, Kneitz S, Bobinger T, Weidemann F, Ertl G, Bauersachs J (2013) Monocytes/macrophages prevent healing defects and left ventricular thrombus formation after myocardial infarction. FASEB J 27(3):871–881. doi:10.1096/fj.12-214049

    CAS  PubMed  Google Scholar 

  • Fujisawa T, Murase K, Kanoh H, Takemura M, Ohnishi H, Seishima M (2012) Adsorptive depletion of CD14(+)CD16(+) proinflammatory monocyte phenotype in patients with generalized pustular psoriasis: clinical efficacy and effects on cytokines. Ther Apher Dial 16(5):436–444. doi:10.1111/j.1744-9987.2012.01108.x

    CAS  PubMed  Google Scholar 

  • Funderburg NT, Zidar DA, Shive C, Lioi A, Mudd J, Musselwhite LW, Simon DI, Costa MA, Rodriguez B, Sieg SF, Lederman MM (2012) Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome. Blood 120(23):4599–4608. doi:10.1182/blood-2012-05-433946

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330(6005):841–845. doi:10.1126/science.1194637

    CAS  PubMed Central  PubMed  Google Scholar 

  • Glass CK, Witztum JL (2001) Atherosclerosis. The road ahead. Cell 104(4):503–516

    CAS  PubMed  Google Scholar 

  • Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3(1):23–35. doi:10.1038/nri978

    CAS  PubMed  Google Scholar 

  • Grage-Griebenow E, Zawatzky R, Kahlert H, Brade L, Flad H, Ernst M (2001) Identification of a novel dendritic cell-like subset of CD64(+)/CD16(+) blood monocytes. Eur J Immunol 31(1):48–56. doi:10.1002/1521-4141(200101)31:1<48::AID-IMMU48>3.0.CO;2-5

    CAS  PubMed  Google Scholar 

  • Haka AS, Potteaux S, Fraser H, Randolph GJ, Maxfield FR (2012) Quantitative analysis of monocyte subpopulations in murine atherosclerotic plaques by multiphoton microscopy. PLoS One 7(9):e44823. doi:10.1371/journal.pone.0044823

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hambleton S, Salem S, Bustamante J, Bigley V, Boisson-Dupuis S, Azevedo J, Fortin A, Haniffa M, Ceron-Gutierrez L, Bacon CM, Menon G, Trouillet C, McDonald D, Carey P, Ginhoux F, Alsina L, Zumwalt TJ, Kong XF, Kumararatne D, Butler K, Hubeau M, Feinberg J, Al-Muhsen S, Cant A, Abel L, Chaussabel D, Doffinger R, Talesnik E, Grumach A, Duarte A, Abarca K, Moraes-Vasconcelos D, Burk D, Berghuis A, Geissmann F, Collin M, Casanova JL, Gros P (2011) IRF8 mutations and human dendritic-cell immunodeficiency. N Engl J Med 365(2):127–138. doi:10.1056/NEJMoa1100066

    CAS  PubMed Central  PubMed  Google Scholar 

  • Han J, Wang B, Han N, Zhao Y, Song C, Feng X, Mao Y, Zhang F, Zhao H, Zeng H (2009) CD14(high)CD16(+) rather than CD14(low)CD16(+) monocytes correlate with disease progression in chronic HIV-infected patients. J Acquir Immune Defic Syndr 52(5):553–559

    CAS  PubMed  Google Scholar 

  • Hanai H, Iida T, Takeuchi K, Watanabe F, Yamada M, Kikuyama M, Maruyama Y, Iwaoka Y, Hirayama K, Nagata S, Takai K (2008) Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease. Am J Gastroenterol 103(5):1210–1216. doi:10.1111/j.1572-0241.2007.01714.x

    PubMed  Google Scholar 

  • Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM, Punt JA, Geissmann F, Hedrick CC (2011) The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C− monocytes. Nat Immunol 12(8):778–785. doi:10.1038/ni.2063

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, Greter M, Mortha A, Boyer SW, Forsberg EC, Tanaka M, van Rooijen N, Garcia-Sastre A, Stanley ER, Ginhoux F, Frenette PS, Merad M (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38(4):792–804. doi:10.1016/j.immuni.2013.04.004

    CAS  PubMed  Google Scholar 

  • Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, Jaworowski A, Crowe SM (2012a) Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11(5):867–875. doi:10.1111/j.1474-9726.2012.00851.x

    CAS  PubMed  Google Scholar 

  • Hearps AC, Maisa A, Cheng WJ, Angelovich TA, Lichtfuss GF, Palmer CS, Landay AL, Jaworowski A, Crowe SM (2012b) HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy. AIDS 26(7):843–853. doi:10.1097/QAD.0b013e328351f756

    CAS  PubMed  Google Scholar 

  • Heimbeck I, Hofer TP, Eder C, Wright AK, Frankenberger M, Marei A, Boghdadi G, Scherberich J, Ziegler-Heitbrock L (2010) Standardized single-platform assay for human monocyte subpopulations: lower CD14+CD16++ monocytes in females. Cytometry A 77(9):823–830. doi:10.1002/cyto.a.20942

    PubMed  Google Scholar 

  • Heine GH, Ulrich C, Seibert E, Seiler S, Marell J, Reichart B, Krause M, Schlitt A, Kohler H, Girndt M (2008) CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients. Kidney Int 73(5):622–629. doi:10.1038/sj.ki.5002744

    CAS  PubMed  Google Scholar 

  • Heine GH, Ortiz A, Massy ZA, Lindholm B, Wiecek A, Martinez-Castelao A, Covic A, Goldsmith D, Suleymanlar G, London GM, Parati G, Sicari R, Zoccali C, Fliser D, European R, Cardiovascular Medicine working group of the European Renal Association-European D, Transplant A (2012) Monocyte subpopulations and cardiovascular risk in chronic kidney disease. Nat Rev Nephrol 8(6):362–369. doi:10.1038/nrneph.2012.41

    CAS  PubMed  Google Scholar 

  • Horelt A, Belge KU, Steppich B, Prinz J, Ziegler-Heitbrock L (2002) The CD14+CD16+ monocytes in erysipelas are expanded and show reduced cytokine production. Eur J Immunol 32(5):1319–1327. doi:10.1002/1521-4141(200205)32:5<1319::AID-IMMU1319>3.0.CO;2-2

    CAS  PubMed  Google Scholar 

  • Horwitz MA (1984) Phagocytosis of the Legionnaires’ disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell 36(1):27–33

    CAS  PubMed  Google Scholar 

  • Hsu AP, Sampaio EP, Khan J, Calvo KR, Lemieux JE, Patel SY, Frucht DM, Vinh DC, Auth RD, Freeman AF, Olivier KN, Uzel G, Zerbe CS, Spalding C, Pittaluga S, Raffeld M, Kuhns DB, Ding L, Paulson ML, Marciano BE, Gea-Banacloche JC, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM (2011) Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 118(10):2653–2655. doi:10.1182/blood-2011-05-356352

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang Y, Yin H, Wang J, Ma X, Zhang Y, Chen K (2012) The significant increase of FcgammaRIIIA (CD16), a sensitive marker, in patients with coronary heart disease. Gene 504(2):284–287. doi:10.1016/j.gene.2012.05.017

    CAS  PubMed  Google Scholar 

  • Ingersoll MA, Spanbroek R, Lottaz C, Gautier EL, Frankenberger M, Hoffmann R, Lang R, Haniffa M, Collin M, Tacke F, Habenicht AJ, Ziegler-Heitbrock L, Randolph GJ (2010) Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115(3):e10–e19. doi:10.1182/blood-2009-07-235028

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iwakami Y, Sakuraba A, Sato T, Takada Y, Izumiya M, Ichikawa H, Hibi T (2009) Granulocyte and monocyte adsorption apheresis therapy modulates monocyte-derived dendritic cell function in patients with ulcerative colitis. Ther Apher Dial 13(2):138–146. doi:10.1111/j.1744-9987.2009.00668.x

    PubMed  Google Scholar 

  • Izikson L, Klein RS, Charo IF, Weiner HL, Luster AD (2000) Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med 192(7):1075–1080

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jakubzick C, Tacke F, Ginhoux F, Wagers AJ, van Rooijen N, Mack M, Merad M, Randolph GJ (2008) Blood monocyte subsets differentially give rise to CD103+ and CD103− pulmonary dendritic cell populations. J Immunol 180(5):3019–3027

    CAS  PubMed  Google Scholar 

  • Jaworowski A, Kamwendo DD, Ellery P, Sonza S, Mwapasa V, Tadesse E, Molyneux ME, Rogerson SJ, Meshnick SR, Crowe SM (2007) CD16+ monocyte subset preferentially harbors HIV-1 and is expanded in pregnant Malawian women with Plasmodium falciparum malaria and HIV-1 infection. J Infect Dis 196(1):38–42. doi:10.1086/518443

    CAS  PubMed  Google Scholar 

  • Jenkins SJ, Ruckerl D, Cook PC, Jones LH, Finkelman FD, van Rooijen N, MacDonald AS, Allen JE (2011) Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science 332(6035):1284–1288. doi:10.1126/science.1204351

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamat A, Misra V, Cassol E, Ancuta P, Yan Z, Li C, Morgello S, Gabuzda D (2012) A plasma biomarker signature of immune activation in HIV patients on antiretroviral therapy. PLoS One 7(2):e30881. doi:10.1371/journal.pone.0030881

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kanai T, Makita S, Kawamura T, Nemoto Y, Kubota D, Nagayama K, Totsuka T, Watanabe M (2007) Extracorporeal elimination of TNF-alpha-producing CD14(dull)CD16(+) monocytes in leukocytapheresis therapy for ulcerative colitis. Inflamm Bowel Dis 13(3):284–290. doi:10.1002/ibd.20017

    PubMed  Google Scholar 

  • Kaplow LS, Goffinet JA (1968) Profound neutropenia during the early phase of hemodialysis. JAMA 203(13):1135–1137

    CAS  PubMed  Google Scholar 

  • Karlmark KR, Weiskirchen R, Zimmermann HW, Gassler N, Ginhoux F, Weber C, Merad M, Luedde T, Trautwein C, Tacke F (2009) Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology 50(1):261–274. doi:10.1002/hep.22950

    CAS  PubMed  Google Scholar 

  • Kashiwagi M, Imanishi T, Tsujioka H, Ikejima H, Kuroi A, Ozaki Y, Ishibashi K, Komukai K, Tanimoto T, Ino Y, Kitabata H, Hirata K, Akasaka T (2010) Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris. Atherosclerosis 212(1):171–176. doi:10.1016/j.atherosclerosis.2010.05.004

    CAS  PubMed  Google Scholar 

  • Katayama K, Matsubara T, Fujiwara M, Koga M, Furukawa S (2000) CD14+CD16+ monocyte subpopulation in Kawasaki disease. Clin Exp Immunol 121(3):566–570

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kawanaka N, Yamamura M, Aita T, Morita Y, Okamoto A, Kawashima M, Iwahashi M, Ueno A, Ohmoto Y, Makino H (2002) CD14+, CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. Arthritis Rheum 46(10):2578–2586. doi:10.1002/art.10545

    CAS  PubMed  Google Scholar 

  • Kim WK, Sun Y, Do H, Autissier P, Halpern EF, Piatak M Jr, Lifson JD, Burdo TH, McGrath MS, Williams K (2010a) Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage. J Leukoc Biol 87(4):557–567. doi:10.1189/jlb.0209082

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim OY, Monsel A, Bertrand M, Coriat P, Cavaillon JM, Adib-Conquy M (2010b) Differential down-regulation of HLA-DR on monocyte subpopulations during systemic inflammation. Crit Care 14(2):R61. doi:10.1186/cc8959

    PubMed Central  PubMed  Google Scholar 

  • Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR (2000) Macrophages in rheumatoid arthritis. Arthritis Res 2(3):189–202. doi:10.1186/ar86

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koren HS, Handwerger BS, Wunderlich JR (1975) Identification of macrophage-like characteristics in a cultured murine tumor line. J Immunol 114(2 pt 2):894–897

    CAS  PubMed  Google Scholar 

  • Korkosz M, Bukowska-Strakova K, Sadis S, Grodzicki T, Siedlar M (2012) Monoclonal antibodies against macrophage colony-stimulating factor diminish the number of circulating intermediate and nonclassical (CD14(++)CD16(+)/CD14(+)CD16(++)) monocytes in rheumatoid arthritis patient. Blood 119(22):5329–5330. doi:10.1182/blood-2012-02-412551

    CAS  PubMed  Google Scholar 

  • Kurihara T, Warr G, Loy J, Bravo R (1997) Defects in macrophage recruitment and host defense in mice lacking the CCR2 chemokine receptor. J Exp Med 186(10):1757–1762

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kwissa M, Nakaya HI, Oluoch H, Pulendran B (2012) Distinct TLR adjuvants differentially stimulate systemic and local innate immune responses in nonhuman primates. Blood 119(9):2044–2055. doi:10.1182/blood-2011-10-388579

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lauber K, Bohn E, Krober SM, Xiao YJ, Blumenthal SG, Lindemann RK, Marini P, Wiedig C, Zobywalski A, Baksh S, Xu Y, Autenrieth IB, Schulze-Osthoff K, Belka C, Stuhler G, Wesselborg S (2003) Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 113(6):717–730

    CAS  PubMed  Google Scholar 

  • Leenen PJ, Jansen AM, van Ewijk W (1986) Murine macrophage cell lines can be ordered in a linear differentiation sequence. Differentiation 32(2):157–164

    CAS  PubMed  Google Scholar 

  • Leenen PJ, Melis M, Slieker WA, Van Ewijk W (1990) Murine macrophage precursor characterization. II. Monoclonal antibodies against macrophage precursor antigens. Eur J Immunol 20(1):27–34. doi:10.1002/eji.1830200105

    CAS  PubMed  Google Scholar 

  • Lenzo JC, Turner AL, Cook AD, Vlahos R, Anderson GP, Reynolds EC, Hamilton JA (2012) Control of macrophage lineage populations by CSF-1 receptor and GM-CSF in homeostasis and inflammation. Immunol Cell Biol 90(4):429–440. doi:10.1038/icb.2011.58

    CAS  PubMed  Google Scholar 

  • Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7(9):678–689. doi:10.1038/nri2156

    CAS  PubMed  Google Scholar 

  • Liaskou E, Zimmermann HW, Li KK, Oo YH, Suresh S, Stamataki Z, Qureshi O, Lalor PF, Shaw J, Syn WK, Curbishley SM, Adams DH (2013) Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics. Hepatology 57(1):385–398. doi:10.1002/hep.26016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Locher C, Vanham G, Kestens L, Kruger M, Ceuppens JL, Vingerhoets J, Gigase P (1994) Expression patterns of Fc gamma receptors, HLA-DR and selected adhesion molecules on monocytes from normal and HIV-infected individuals. Clin Exp Immunol 98(1):115–122

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lundahl J, Hallden G, Hallgren M, Skold CM, Hed J (1995) Altered expression of CD11b/CD18 and CD62L on human monocytes after cell preparation procedures. J Immunol Methods 180(1):93–100

    CAS  PubMed  Google Scholar 

  • MacDonald KP, Palmer JS, Cronau S, Seppanen E, Olver S, Raffelt NC, Kuns R, Pettit AR, Clouston A, Wainwright B, Branstetter D, Smith J, Paxton RJ, Cerretti DP, Bonham L, Hill GR, Hume DA (2010) An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation. Blood 116(19):3955–3963. doi:10.1182/blood-2010-02-266296

    CAS  PubMed  Google Scholar 

  • Maekawa Y, Anzai T, Yoshikawa T, Asakura Y, Takahashi T, Ishikawa S, Mitamura H, Ogawa S (2002) Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction: a possible role for left ventricular remodeling. J Am Coll Cardiol 39(2):241–246

    PubMed  Google Scholar 

  • Mertz KD, Junt T, Schmid M, Pfaltz M, Kempf W (2010) Inflammatory monocytes are a reservoir for Merkel cell polyomavirus. J Invest Dermatol 130(4):1146–1151. doi:10.1038/jid.2009.392

    CAS  PubMed  Google Scholar 

  • Mikolajczyk TP, Skrzeczynska-Moncznik JE, Zarebski MA, Marewicz EA, Wisniewska AM, Dzieba M, Dobrucki JW, Pryjma JR (2009) Interaction of human peripheral blood monocytes with apoptotic polymorphonuclear cells. Immunology 128(1):103–113. doi:10.1111/j.1365-2567.2009.03087.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mosig S, Rennert K, Krause S, Kzhyshkowska J, Neunubel K, Heller R, Funke H (2009) Different functions of monocyte subsets in familial hypercholesterolemia: potential function of CD14+ CD16+ monocytes in detoxification of oxidized LDL. FASEB J 23(3):866–874. doi:10.1096/fj.08-118240

    CAS  PubMed  Google Scholar 

  • Munn DH, Garnick MB, Cheung NK (1990) Effects of parenteral recombinant human macrophage colony-stimulating factor on monocyte number, phenotype, and antitumor cytotoxicity in nonhuman primates. Blood 75(10):2042–2048

    CAS  PubMed  Google Scholar 

  • Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, Power CA (2000) International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52(1):145–176

    CAS  PubMed  Google Scholar 

  • Nageh MF, Sandberg ET, Marotti KR, Lin AH, Melchior EP, Bullard DC, Beaudet AL (1997) Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice. Arterioscler Thromb Vasc Biol 17(8):1517–1520

    CAS  PubMed  Google Scholar 

  • Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204(12):3037–3047. doi:10.1084/jem.20070885

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nockher WA, Scherberich JE (1998) Expanded CD14+ CD16+ monocyte subpopulation in patients with acute and chronic infections undergoing hemodialysis. Infect Immun 66(6):2782–2790

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nockher WA, Wiemer J, Scherberich JE (2001) Haemodialysis monocytopenia: differential sequestration kinetics of CD14+CD16+ and CD14++ blood monocyte subsets. Clin Exp Immunol 123(1):49–55

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nyugen J, Agrawal S, Gollapudi S, Gupta S (2010) Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol 30(6):806–813. doi:10.1007/s10875-010-9448-8

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pachot A, Cazalis MA, Venet F, Turrel F, Faudot C, Voirin N, Diasparra J, Bourgoin N, Poitevin F, Mougin B, Lepape A, Monneret G (2008) Decreased expression of the fractalkine receptor CX3CR1 on circulating monocytes as new feature of sepsis-induced immunosuppression. J Immunol 180(9):6421–6429

    CAS  PubMed  Google Scholar 

  • Palframan RT, Jung S, Cheng G, Weninger W, Luo Y, Dorf M, Littman DR, Rollins BJ, Zweerink H, Rot A, von Andrian UH (2001) Inflammatory chemokine transport and presentation in HEV: a remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues. J Exp Med 194(9):1361–1373

    CAS  PubMed Central  PubMed  Google Scholar 

  • Passlick B, Flieger D, Ziegler-Heitbrock HW (1989) Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74(7):2527–2534

    CAS  PubMed  Google Scholar 

  • Perry SE, Mostafa SM, Wenstone R, Shenkin A, McLaughlin PJ (2003) Is low monocyte HLA-DR expression helpful to predict outcome in severe sepsis? Intensive Care Med 29(8):1245–1252. doi:10.1007/s00134-003-1686-2

    PubMed  Google Scholar 

  • Pforte A, Brunner A, Gais P, Burger G, Breyer G, Strobel M, Haussinger K, Ziegler-Heitbrock HW (1993) Concomitant modulation of serum-soluble interleukin-2 receptor and alveolar macrophage interleukin-2 receptor in sarcoidosis. Am Rev Respir Dis 147(3):717–722. doi:10.1164/ajrccm/147.3.717

    CAS  PubMed  Google Scholar 

  • Poitou C, Dalmas E, Renovato M, Benhamo V, Hajduch F, Abdennour M, Kahn JF, Veyrie N, Rizkalla S, Fridman WH, Sautes-Fridman C, Clement K, Cremer I (2011) CD14dimCD16+ and CD14+CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis. Arterioscler Thromb Vasc Biol 31(10):2322–2330. doi:10.1161/ATVBAHA.111.230979

    CAS  PubMed  Google Scholar 

  • Potteaux S, Gautier EL, Hutchison SB, van Rooijen N, Rader DJ, Thomas MJ, Sorci-Thomas MG, Randolph GJ (2011) Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe−/− mice during disease regression. J Clin Invest 121(5):2025–2036. doi:10.1172/JCI43802

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ralph P, Nakoinz I, Raschke WC (1974) Lymphosarcoma cell growth is selectively inhibited by B lymphocyte mitogens: LPS, dextran sulfate and PPD. Biochem Biophys Res Commun 61(4):1268–1275

    CAS  PubMed  Google Scholar 

  • Ralph P, Prichard J, Cohn M (1975) Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J Immunol 114(2 pt 2):898–905

    CAS  PubMed  Google Scholar 

  • Raschke WC, Baird S, Ralph P, Nakoinz I (1978) Functional macrophage cell lines transformed by Abelson leukemia virus. Cell 15(1):261–267

    CAS  PubMed  Google Scholar 

  • Ridker PM (2007) C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol 49(21):2129–2138. doi:10.1016/j.jacc.2007.02.052

    CAS  PubMed  Google Scholar 

  • Rogacev KS, Ulrich C, Blomer L, Hornof F, Oster K, Ziegelin M, Cremers B, Grenner Y, Geisel J, Schlitt A, Kohler H, Fliser D, Girndt M, Heine GH (2010) Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J 31(3):369–376. doi:10.1093/eurheartj/ehp308

    CAS  PubMed  Google Scholar 

  • Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P, Grosse-Dunker G, Heisel I, Hornof F, Jeken J, Rebling NM, Ulrich C, Scheller B, Bohm M, Fliser D, Heine GH (2012) CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 60(16):1512–1520. doi:10.1016/j.jacc.2012.07.019

    CAS  PubMed  Google Scholar 

  • Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340(2):115–126. doi:10.1056/NEJM199901143400207

    CAS  PubMed  Google Scholar 

  • Rossol M, Kraus S, Pierer M, Baerwald C, Wagner U (2012) The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population. Arthritis Rheum 64(3):671–677. doi:10.1002/art.33418

    CAS  PubMed  Google Scholar 

  • Saionji K, Ohsaka A (2001) Expansion of CD4+CD16+ blood monocytes in patients with chronic renal failure undergoing dialysis: possible involvement of macrophage colony-stimulating factor. Acta Haematol 105(1):21–26. doi:10.1159/000046528

  • Saleh MN, Goldman SJ, LoBuglio AF, Beall AC, Sabio H, McCord MC, Minasian L, Alpaugh RK, Weiner LM, Munn DH (1995) CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor. Blood 85(10):2910–2917

    CAS  PubMed  Google Scholar 

  • Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179(4):1109–1118

    CAS  PubMed  Google Scholar 

  • Sanchez C, Domenech N, Vazquez J, Alonso F, Ezquerra A, Dominguez J (1999) The porcine 2A10 antigen is homologous to human CD163 and related to macrophage differentiation. J Immunol 162(9):5230–5237

    CAS  PubMed  Google Scholar 

  • Sanchez-Torres C, Garcia-Romo GS, Cornejo-Cortes MA, Rivas-Carvalho A, Sanchez-Schmitz G (2001) CD16+ and CD16− human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells. Int Immunol 13(12):1571–1581

    CAS  PubMed  Google Scholar 

  • Santiago-Raber ML, Amano H, Amano E, Baudino L, Otani M, Lin Q, Nimmerjahn F, Verbeek JS, Ravetch JV, Takasaki Y, Hirose S, Izui S (2009) Fcgamma receptor-dependent expansion of a hyperactive monocyte subset in lupus-prone mice. Arthritis Rheum 60(8):2408–2417. doi:10.1002/art.24787

    CAS  PubMed  Google Scholar 

  • Santiago-Raber ML, Baudino L, Alvarez M, van Rooijen N, Nimmerjahn F, Izui S (2011) TLR7/9-mediated monocytosis and maturation of Gr-1(hi) inflammatory monocytes towards Gr-1(lo) resting monocytes implicated in murine lupus. J Autoimmun 37(3):171–179. doi:10.1016/j.jaut.2011.05.015

    CAS  PubMed  Google Scholar 

  • Scatizzi JC, Hutcheson J, Bickel E, Woods JM, Klosowska K, Moore TL, Haines GK 3rd, Perlman H (2006) p21Cip1 is required for the development of monocytes and their response to serum transfer-induced arthritis. Am J Pathol 168(5):1531–1541. doi:10.2353/ajpath.2006.050555

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schauer D, Starlinger P, Reiter C, Jahn N, Zajc P, Buchberger E, Bachleitner-Hofmann T, Bergmann M, Stift A, Gruenberger T, Brostjan C (2012) Intermediate monocytes but not TIE2-expressing monocytes are a sensitive diagnostic indicator for colorectal cancer. PLoS One 7(9):e44450. doi:10.1371/journal.pone.0044450

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schulz C, Gomez Perdiguero E, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SE, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336(6077):86–90. doi:10.1126/science.1219179

    CAS  PubMed  Google Scholar 

  • Scriba A, Schneider M, Grau V, van der Meide PH, Steiniger B (1997) Rat monocytes up-regulate NKR-P1A and down-modulate CD4 and CD43 during activation in vivo: monocyte subpopulations in normal and IFN-gamma-treated rats. J Leukoc Biol 62(6):741–752

    CAS  PubMed  Google Scholar 

  • Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F (2010) Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol 11:30. doi:10.1186/1471-2172-11-30

    PubMed Central  PubMed  Google Scholar 

  • Seidler S, Zimmermann HW, Weiskirchen R, Trautwein C, Tacke F (2012) Elevated circulating soluble interleukin-2 receptor in patients with chronic liver diseases is associated with non-classical monocytes. BMC Gastroenterol 12:38. doi:10.1186/1471-230X-12-38

    CAS  PubMed Central  PubMed  Google Scholar 

  • Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, Lopez CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S A 110(9):3507–3512. doi:10.1073/pnas.1222878110

    CAS  PubMed Central  PubMed  Google Scholar 

  • Serbina NV, Pamer EG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7(3):311–317. doi:10.1038/ni1309

    CAS  PubMed  Google Scholar 

  • Sester U, Sester M, Heine G, Kaul H, Girndt M, Kohler H (2001) Strong depletion of CD14(+)CD16(+) monocytes during haemodialysis treatment. Nephrol Dial Transplant 16(7): 1402–1408

    CAS  PubMed  Google Scholar 

  • Shalova IN, Kajiji T, Lim JY, Gomez-Pina V, Fernandez-Ruiz I, Arnalich F, Iau PT, Lopez-Collazo E, Wong SC, Biswas SK (2012) CD16 regulates TRIF-dependent TLR4 response in human monocytes and their subsets. J Immunol 188(8):3584–3593. doi:10.4049/jimmunol.1100244

    CAS  PubMed  Google Scholar 

  • Siedlar M, Strach M, Bukowska-Strakova K, Lenart M, Szaflarska A, Weglarczyk K, Rutkowska M, Baj-Krzyworzeka M, Pituch-Noworolska A, Kowalczyk D, Grodzicki T, Ziegler-Heitbrock L, Zembala M (2011) Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients. Clin Immunol 139(2):122–132. doi:10.1016/j.clim.2011.01.002

    CAS  PubMed  Google Scholar 

  • Skrzeczynska J, Kobylarz K, Hartwich Z, Zembala M, Pryjma J (2002) CD14+CD16+ monocytes in the course of sepsis in neonates and small children: monitoring and functional studies. Scand J Immunol 55(6):629–638

    CAS  PubMed  Google Scholar 

  • Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M (1995) Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci U S A 92(18):8264–8268

    CAS  PubMed Central  PubMed  Google Scholar 

  • Steppich B, Dayyani F, Gruber R, Lorenz R, Mack M, Ziegler-Heitbrock HW (2000) Selective mobilization of CD14(+)CD16(+) monocytes by exercise. Am J Physiol Cell Physiol 279(3):C578–C586

    CAS  PubMed  Google Scholar 

  • Stuard S, Carreno MP, Poignet JL, Albertazzi A, Haeffner-Cavaillon N (1995) A major role for CD62P/CD15s interaction in leukocyte margination during hemodialysis. Kidney Int 48(1):93–102

    CAS  PubMed  Google Scholar 

  • Subimerb C, Pinlaor S, Lulitanond V, Khuntikeo N, Okada S, McGrath MS, Wongkham S (2010) Circulating CD14(+) CD16(+) monocyte levels predict tissue invasive character of cholangiocarcinoma. Clin Exp Immunol 161(3):471–479. doi:10.1111/j.1365-2249.2010.04200.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sunderkotter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ (2004) Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 172(7):4410–4417

    PubMed  Google Scholar 

  • Sundstrom C, Nilsson K (1976) Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer 17(5):565–577

    CAS  PubMed  Google Scholar 

  • Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ (2007) Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. J Clin Invest 117(1):195–205. doi:10.1172/JCI29950

    CAS  PubMed Central  PubMed  Google Scholar 

  • Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ (2009) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325(5940):612–616. doi:10.1126/science.1175202

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tacke F (2012) Functional role of intrahepatic monocyte subsets for the progression of liver inflammation and liver fibrosis in vivo. Fibrogenesis Tissue Repair 5(Suppl 1):S27. doi:10.1186/1755-1536-5-S1-S27

    PubMed Central  PubMed  Google Scholar 

  • Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, Garin A, Liu J, Mack M, van Rooijen N, Lira SA, Habenicht AJ, Randolph GJ (2007) Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 117(1):185–194. doi:10.1172/JCI28549

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thomas ED, Ramberg RE, Sale GE, Sparkes RS, Golde DW (1976) Direct evidence for a bone marrow origin of the alveolar macrophage in man. Science 192(4243):1016–1018

    CAS  PubMed  Google Scholar 

  • Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K (1980) Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer 26(2):171–176

    CAS  PubMed  Google Scholar 

  • Tsujioka H, Imanishi T, Ikejima H, Kuroi A, Takarada S, Tanimoto T, Kitabata H, Okochi K, Arita Y, Ishibashi K, Komukai K, Kataiwa H, Nakamura N, Hirata K, Tanaka A, Akasaka T (2009) Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. J Am Coll Cardiol 54(2):130–138. doi:10.1016/j.jacc.2009.04.021

    PubMed  Google Scholar 

  • Tsujioka H, Imanishi T, Ikejima H, Tanimoto T, Kuroi A, Kashiwagi M, Okochi K, Ishibashi K, Komukai K, Ino Y, Kitabata H, Akasaka T (2010) Post-reperfusion enhancement of CD14(+)CD16(−) monocytes and microvascular obstruction in ST-segment elevation acute myocardial infarction. Circ J 74(6):1175–1182

    PubMed  Google Scholar 

  • Underhill DM, Ozinsky A (2002) Phagocytosis of microbes: complexity in action. Annu Rev Immunol 20:825–852. doi:10.1146/annurev.immunol.20.103001.114744

    CAS  PubMed  Google Scholar 

  • van Amerongen MJ, Harmsen MC, van Rooijen N, Petersen AH, van Luyn MJ (2007) Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am J Pathol 170(3):818–829. doi:10.2353/ajpath.2007.060547

    PubMed Central  PubMed  Google Scholar 

  • van Furth R, Cohn ZA (1968) The origin and kinetics of mononuclear phagocytes. J Exp Med 128(3):415–435

    PubMed Central  PubMed  Google Scholar 

  • van Rooijen N, Hendrikx E (2010) Liposomes for specific depletion of macrophages from organs and tissues. Methods Mol Biol 605:189–203. doi:10.1007/978-1-60327-360-2_13

    PubMed  Google Scholar 

  • Varol C, Landsman L, Fogg DK, Greenshtein L, Gildor B, Margalit R, Kalchenko V, Geissmann F, Jung S (2007) Monocytes give rise to mucosal, but not splenic, conventional dendritic cells. J Exp Med 204(1):171–180. doi:10.1084/jem.20061011

    CAS  PubMed Central  PubMed  Google Scholar 

  • Venet F, Tissot S, Debard AL, Faudot C, Crampe C, Pachot A, Ayala A, Monneret G (2007) Decreased monocyte human leukocyte antigen-DR expression after severe burn injury: correlation with severity and secondary septic shock. Crit Care Med 35(8):1910–1917. doi:10.1097/01.CCM.0000275271.77350.B6

    CAS  PubMed  Google Scholar 

  • Vergunst CE, Gerlag DM, Lopatinskaya L, Klareskog L, Smith MD, van den Bosch F, Dinant HJ, Lee Y, Wyant T, Jacobson EW, Baeten D, Tak PP (2008) Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 58(7):1931–1939. doi:10.1002/art.23591

    CAS  PubMed  Google Scholar 

  • Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF, Olivier KN, Spalding C, Hughes S, Pittaluga S, Raffeld M, Sorbara LR, Elloumi HZ, Kuhns DB, Turner ML, Cowen EW, Fink D, Long-Priel D, Hsu AP, Ding L, Paulson ML, Whitney AR, Sampaio EP, Frucht DM, DeLeo FR, Holland SM (2010) Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood 115(8):1519–1529. doi:10.1182/blood-2009-03-208629

    CAS  PubMed Central  PubMed  Google Scholar 

  • Volk HD, Reinke P, Krausch D, Zuckermann H, Asadullah K, Muller JM, Docke WD, Kox WJ (1996) Monocyte deactivation—rationale for a new therapeutic strategy in sepsis. Intensive Care Med 22(Suppl 4):S474–S481

    PubMed  Google Scholar 

  • Warner NL, Moore MA, Metcalf D (1969) A transplantable myelomonocytic leukemia in BALB-c mice: cytology, karyotype, and muramidase content. J Natl Cancer Inst 43(4):963–982

    CAS  PubMed  Google Scholar 

  • Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M, Frankenberger M, Weber KS, Ziegler-Heitbrock HW (2000) Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol 67(5):699–704

    CAS  PubMed  Google Scholar 

  • Weiner LM, Li W, Holmes M, Catalano RB, Dovnarsky M, Padavic K, Alpaugh RK (1994) Phase I trial of recombinant macrophage colony-stimulating factor and recombinant gamma-interferon: toxicity, monocytosis, and clinical effects. Cancer Res 54(15):4084–4090

    CAS  PubMed  Google Scholar 

  • Werz O, Schneider N, Brungs M, Sailer ER, Safayhi H, Ammon HP, Steinhilber D (1997) A test system for leukotriene synthesis inhibitors based on the in-vitro differentiation of the human leukemic cell lines HL-60 and Mono Mac 6. Naunyn Schmiedebergs Arch Pharmacol 356(4):441–445

    CAS  PubMed  Google Scholar 

  • Werz O, Klemm J, Samuelsson B, Radmark O (2000) 5-Lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases. Proc Natl Acad Sci U S A 97(10):5261–5266. doi:10.1073/pnas.050588997

    CAS  PubMed Central  PubMed  Google Scholar 

  • West SD, Goldberg D, Ziegler A, Krencicki M, Du Clos TW, Mold C (2012) Transforming growth factor-beta, macrophage colony-stimulating factor and C-reactive protein levels correlate with CD14(high)CD16+ monocyte induction and activation in trauma patients. PLoS One 7(12):e52406. doi:10.1371/journal.pone.0052406

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wheeler JG, Mussolino ME, Gillum RF, Danesh J (2004) Associations between differential leucocyte count and incident coronary heart disease: 1764 incident cases from seven prospective studies of 30,374 individuals. Eur Heart J 25(15):1287–1292. doi:10.1016/j.ehj.2004.05.002

    PubMed  Google Scholar 

  • Whitelaw DM (1972) Observations on human monocyte kinetics after pulse labeling. Cell Tissue Kinet 5(4):311–317

    CAS  PubMed  Google Scholar 

  • Wiktor-Jedrzejczak WW, Ahmed A, Szczylik C, Skelly RR (1982) Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation. J Exp Med 156(5):1516–1527

    CAS  PubMed  Google Scholar 

  • Wong KL, Chen W, Balakrishnan T, Toh YX, Fink K, Wong SC (2012) Susceptibility and response of human blood monocyte subsets to primary dengue virus infection. PLoS One 7(5):e36435. doi:10.1371/journal.pone.0036435

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu HP, Shih CC, Lin CY, Hua CC, Chuang DY (2011) Serial increase of IL-12 response and human leukocyte antigen-DR expression in severe sepsis survivors. Crit Care 15(5):R224. doi:10.1186/cc10464

    PubMed Central  PubMed  Google Scholar 

  • Yasaka T, Mantich NM, Boxer LA, Baehner RL (1981) Functions of human monocyte and lymphocyte subsets obtained by countercurrent centrifugal elutriation: differing functional capacities of human monocyte subsets. J Immunol 127(4):1515–1518

    CAS  PubMed  Google Scholar 

  • Ylitalo R, Oksala O, Yla-Herttuala S, Ylitalo P (1994) Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med 123(5):769–776

    CAS  PubMed  Google Scholar 

  • Yona S, Kim KW, Wolf Y, Mildner A, Varol D, Breker M, Strauss-Ayali D, Viukov S, Guilliams M, Misharin A, Hume DA, Perlman H, Malissen B, Zelzer E, Jung S (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38(1):79–91. doi:10.1016/j.immuni.2012.12.001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD, Nishikawa S (1990) The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345(6274):442–444. doi:10.1038/345442a0

    CAS  PubMed  Google Scholar 

  • Yrlid U, Jenkins CD, MacPherson GG (2006) Relationships between distinct blood monocyte subsets and migrating intestinal lymph dendritic cells in vivo under steady-state conditions. J Immunol 176(7):4155–4162

    CAS  PubMed  Google Scholar 

  • Zawada AM, Rogacev KS, Rotter B, Winter P, Marell RR, Fliser D, Heine GH (2011) SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood 118(12):e50–e61. doi:10.1182/blood-2011-01-326827

    CAS  PubMed  Google Scholar 

  • Zembala M, Uracz W, Ruggiero I, Mytar B, Pryjma J (1984) Isolation and functional characteristics of FcR+ and FcR− human monocyte subsets. J Immunol 133(3):1293–1299

    CAS  PubMed  Google Scholar 

  • Zhao C, Zhang H, Wong WC, Sem X, Han H, Ong SM, Tan YC, Yeap WH, Gan CS, Ng KQ, Koh MB, Kourilsky P, Sze SK, Wong SC (2009) Identification of novel functional differences in monocyte subsets using proteomic and transcriptomic methods. J Proteome Res 8(8):4028–4038. doi:10.1021/pr900364p

    CAS  PubMed  Google Scholar 

  • Zhong H, Bao W, Li X, Miller A, Seery C, Haq N, Bussel J, Yazdanbakhsh K (2012) CD16+ monocytes control T-cell subset development in immune thrombocytopenia. Blood 120(16):3326–3335. doi:10.1182/blood-2012-06-434605

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ziegler-Heitbrock L (2007) The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 81(3):584–592. doi:10.1189/jlb.0806510

    CAS  PubMed  Google Scholar 

  • Ziegler-Heitbrock L, Hofer TP (2013) Toward a refined definition of monocyte subsets. Front Immunol 4:23. doi:10.3389/fimmu.2013.00023

    PubMed Central  PubMed  Google Scholar 

  • Ziegler-Heitbrock HW, Thiel E, Futterer A, Herzog V, Wirtz A, Riethmuller G (1988) Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes. Int J Cancer 41(3):456–461

    CAS  PubMed  Google Scholar 

  • Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, Leenen PJ, Liu YJ, MacPherson G, Randolph GJ, Scherberich J, Schmitz J, Shortman K, Sozzani S, Strobl H, Zembala M, Austyn JM, Lutz MB (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116(16):e74–e80. doi:10.1182/blood-2010-02-258558

    CAS  PubMed  Google Scholar 

  • Zimmermann HW, Seidler S, Nattermann J, Gassler N, Hellerbrand C, Zernecke A, Tischendorf JJ, Luedde T, Weiskirchen R, Trautwein C, Tacke F (2010) Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis. PLoS One 5(6):e11049. doi:10.1371/journal.pone.0011049

    PubMed Central  PubMed  Google Scholar 

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Acknowledgments

I thank Thomas Hofer, Gauting, Germany, Pieter Leenen, Rotterdam, The Netherlands, Gunnar Heine, Homburg, Germany, and Hans Dieter Volk, Berlin, Germany, for helpful discussion.

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  1. Helmholtz Zentrum Muenchen, Robert-Koch-Allee 1, 82131, Gauting, Germany

    Loems Ziegler-Heitbrock

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  1. Loems Ziegler-Heitbrock
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Correspondence to Loems Ziegler-Heitbrock .

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  1. Singapore Immunology Network (SIgN) Biomedical Sciences Institutes, A*STAR, Singapore, Singapore

    Subhra K. Biswas

  2. IRCCS Humanitas Clinical and Research Institute, Humanitas University, Rozzano, Italy

    Alberto Mantovani

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Ziegler-Heitbrock, L. (2014). Blood Monocytes and Their Subsets in Health and Disease. In: Biswas, S., Mantovani, A. (eds) Macrophages: Biology and Role in the Pathology of Diseases. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1311-4_1

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