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Handbook of Immunosenescence pp 1–16Cite as

Signal Transduction Changes in Human Neutrophils with Age

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Abstract

The role of innate immune cells as first line of defense against pathogens and foreign invasion has been widely recognized. Among the innate immune cells, neutrophils represent the most potent phagocytic cell and possess an elaborate arsenal capable of efficiently neutralizing pathogens; in addition, neutrophils modulate adaptive immunity by secreting cytokines. Over the years, it has become clear that human aging negatively affects neutrophils’ responses. A common alteration underlying these functional changes in aging is the decrease of phosphorylated forms of signaling molecules after receptor engagement. The consequences of aging on human neutrophils may impair the activation of immune responses and contribute to poorer vaccine responses and greater morbidity and mortality from infectious diseases in older adults. This chapter describes our current knowledge of the age-related alterations in receptors for the Nformyl-met-leu-phe (fMLP) peptide, for the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), and for Toll-like receptors (TLR) and triggering receptor expressed on myeloid cells-1 (TREM-1).

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References

  • Alemán OR, Mora N, Cortes-Vieyra R, Uribe-Querol E, Rosales C (2016) Differential use of human neutrophil Fcγ receptors for inducing neutrophil extracellular trap formation. J Immunol Res 2016:2908034

    Article  PubMed  PubMed Central  Google Scholar 

  • Alvarez E, Ruiz-Guttierrez V, Sobrino F, Santa-María C (2001) Age-related changes in membrane lipid composition, fluidity and respiratory burst in rat peripheral neutrophils. Clin Exp Immunol 124(1):95–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Altznauer F, Martinelli S, Yousefi S, Thürig C, Schmid I, Conway EM, Schöni MH, Vogt P, Mueller C, Fey MF, Zangemeister-Wittke U, Simon HU (2004) Inflammation-associated cell cycle-independent block of apoptosis by survivin in terminally differentiated neutrophils. J Exp Med 199(10):1343–54

    Google Scholar 

  • Arts RJ, Joosten LA, van der Meer JW, Netea MG (2013) TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol 93(2):209–215

    Article  CAS  PubMed  Google Scholar 

  • Balasubramanian N, Advani SH, Zingde SM (2002) Protein kinase C isoforms in normal and leukemic neutrophils: altered levels in leukemic neutrophils and changes during myeloid maturation in chronic myeloid leukemia. Leukemia Res 26(1):67–81

    Article  CAS  Google Scholar 

  • Berger M, Hsieh CY, Bakele M, Marcos V, Rieber N, Kormann M, Mays L, Hofer L, Neth O, Vitkov L, Krautgartner WD, von Schweinitz D, Kappler R, Hector A, Weber A, Hartl D (2012) Neutrophils express distinct RNA receptors in a non-canonical way. J Biol Chem 287(23): 19409–19417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biasi D, Carletto A, Dellagnola C et al (1996) Neutrophil migration, oxidative metabolism, and adhesion in elderly and young subjects. Inflammation 20(6):673–681

    Article  CAS  PubMed  Google Scholar 

  • Bleharski JR, Kiessler V, Buonsanti C, Sieling PA, Stenger S, Colonna M, Modlin RL (2003) A role for triggering receptor expressed on myeloid cells-1 in host defense during the early-induced and adaptive phases of the immune response. J Immunol 170(7):3812–3818

    Article  CAS  PubMed  Google Scholar 

  • Bouchon A, Dietrich J, Colonna M (2000) Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes. J Immunol 164(10): 4991–4995

    Article  CAS  PubMed  Google Scholar 

  • Camps M, Carozzi A, Schnabel P, Scheer A, Parker PJ, Gierschik P (1992) Isozyme-selective stimulation of phospholipase C-b2 by G protein b g subunits. Nature 360(6405):684–689

    Article  CAS  PubMed  Google Scholar 

  • Cannon JP, O’Driscoll M, Litman GW (2012) Specific lipid recognition is a general feature of CD300 and TREM molecules. Immunogenetics 64(1):39–47

    Article  CAS  PubMed  Google Scholar 

  • Chang LC, Wang JP (1999) Examination of the signal transduction pathways leading to activation of extracellular signal-regulated kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. FEBS Lett 454(1–2):165–168

    Article  CAS  PubMed  Google Scholar 

  • Chang LC, Wang JP (2000) Activation of p38 mitogen-activated protein kinase by formyl-methionyl-leucyl-phenylalanine in rat neutrophils. Eur J Pharmacol 390(1–2):61–66

    Article  CAS  PubMed  Google Scholar 

  • Cloutier A, Ear T, Blais-Charron E, Dubois CM, McDonald PP (2007) Differential involvement of NF-kappaB and MAP kinase pathways in the generation of inflammatory cytokines by human neutrophils. J Leukoc Biol 81(2):567–577

    Article  CAS  PubMed  Google Scholar 

  • Dalboni TM, Abe AE, de Oliveira CE, Lara VS, Campanelli AP, Gasparoto CT, Gasparoto TH (2013) Activation profile of CXCL8-stimulated neutrophils and aging. Cytokine 61(3):716–719

    Article  CAS  PubMed  Google Scholar 

  • Ear T, Fortin CF, Simard A et al (2010) Constitutive association of TGF-beta-activated kinase 1 with the IkappaB kinase complex in the nucleus and cytoplasm of human neutrophils and its impact on downstream processes. J Immunol 184(7):3897–3906

    Article  CAS  PubMed  Google Scholar 

  • Epling-Burnette PK, Zhong B, Bai F, Jiang K, Bailey RD, Garcia R, Jove R, Djeu JY, Loughran TP Jr, Wei S (2001) Cooperative regulation of Mcl-1 by Janus kinase/stat and phosphatidylinositol 3-kinase contribute to granulocyte-macrophage colony-stimulating factor-delayed apoptosis in human neutrophils. J Immunol 166(12):7486–95

    Google Scholar 

  • Fortin C, Fulop T (2015) Isolation of lipid rafts from human neutrophils by density gradient centrifugation. Methods Mol Biol 1343:1–7

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, Larbi A, Lesur O, Douziech N, Fulop T (2006) Impairment of SHP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions. J Leukoc Biol 79(5):1061–1072

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, Larbi A, Dupuis G, Lesur O, Fulop T (2007a) GM-CSF activates the Jak/STAT pathway to rescue polymorphonuclear neutrophils from spontaneous apoptosis in young but not elderly individuals. Biogerontology 8(2):173–187

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, Lesur O, Fulop T (2007b) Effects of TREM-1 activation in human neutrophils: activation of signaling pathways, recruitment into lipid rafts and association with TLR4. Int Immunol 19(1):41–50

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, Lesur O, Fulop T (2007c) Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions. FEBS Lett 581(6):1173–1178

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, McDonald PP, Lesur O, Fülöp T Jr (2008) Aging and neutrophils: there is still much to do. Rejuvenation Res 11(5):873–882

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, Cloutier A, Ear T, Sylvain-Prévost S, Mayer TZ, Bouchelaghem R, McDonald PP (2011) A class IA PI3K controls inflammatory cytokine production in human neutrophils. Eur J Immunol 41(6):1709–1719

    Article  CAS  PubMed  Google Scholar 

  • Fortin CF, Mayer TZ, Cloutier A, McDonald PP (2013) Translational control of human neutrophil responses by MNK1. J Leukoc Biol 94(4):693–703

    Article  CAS  PubMed  Google Scholar 

  • Fu H, Karlsson J, Bylund J, Movitz C, Karlsson A, Dahlgren C (2006) Ligand recognition and activation of formyl peptide receptors in neutrophils. J Leukoc Biol 79(2):247–256

    Article  CAS  PubMed  Google Scholar 

  • Fülöp T Jr, Fóris G, Wórum I, Leövey A (1985) Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes. Clin Exp Immunol 61(2):425–432

    PubMed  PubMed Central  Google Scholar 

  • Fulop T Jr, Fouquet C, Allaire P, Perrin N, Lacombe G, Stankova J, Rola-Pleszczinsky M, Wagner JR, Khalil A, Dupuis G (1997) Changes in apoptosis of human polymorphonuclear granulocytes with ageing. Mech Ageing Dev 96(1–3):15–31

    Article  CAS  PubMed  Google Scholar 

  • Fulop T, Larbi A, Douziech N, Fortin CF, Guerard KP, Lesur O, Khalil A, Dupuis G, Fulop T (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell 3(4):217–226

    Article  CAS  PubMed  Google Scholar 

  • Futosi K, Fodor S, Mócsai A (2013) Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol 17(3):638–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geijsen N, Koenderman L, Coffer PJ (2001) Specificity in cytokine signal transduction: lessons learned from the IL-3/IL-5/GM-CSF. Cytokine Growth Factor Rev 12(1):19–25

    Article  CAS  PubMed  Google Scholar 

  • Gibot S (2006) The therapeutic potential of TREM-1 modulation in the treatment of sepsis and beyond. Curr Opin Investig Drugs 7(5):438–442

    CAS  PubMed  Google Scholar 

  • Gibot S, Kolopp-Sarda MN, Bene MC, Cravoisy A, Levy B, Faure GC, Bollaert PE (2004) Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis. Ann Intern Med 141(1):9–15

    Article  CAS  PubMed  Google Scholar 

  • Gibot S, Buonsanti C, Massin F, Romano M, Kolopp-Sarda MN, Benigni F, Faure GC, Béné MC, Panina-Bordignon P, Passini N, Lévy B (2006) Modulation of the triggering receptor expressed on the myeloid cell type 1 pathway in murine septic shock. Infect Immun 74(5):2823–2830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gierschik P, Sidoropoulos D, Jakobs KH (1989) Two distinct Gi-proteins mediate formyl peptide receptor signal transduction in human leukemia (HL-60) cells. J Biol Chem 264(36): 21470–21473

    CAS  PubMed  Google Scholar 

  • Hazeldine J, Harris P, Chapple IL, Grant M, Greenwood H, Livesey A, Sapey E, Lord JM (2014) Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals. Aging Cell 13(4):690–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Indelicato SR, Udupa KB, Balazovich KJ, Boxer LA, Lipschitz DA (1990) Effect of age on phorbol-ester stimulation of human neutrophils. J Gerontol 45(3):B75–B80

    Article  CAS  PubMed  Google Scholar 

  • Juss JK, Hayhoe RP, Owen CE, Bruce I, Walmsley SR, Cowburn AS, Kulkarni S, Boyle KB, Stephens L, Hawkins PT, Chilvers ER, Condliffe AM (2012) Functional redundancy of class I phosphoinositide 3-kinase (PI3K) isoforms in signaling growth factor-mediated human neutrophil survival. PLoS One 7(9):e45933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalyan S, Kabelitz D (2014) When neutrophils meet T cells: beginnings of a tumultuous relationship with underappreciated potential. Eur J Immunol 44(3):627–633

    Article  CAS  PubMed  Google Scholar 

  • Kindzelskii AL, Sitrin RG, Petty HR (2004) Cutting edge: optical microspectrophotometry supports the existence of gel phase lipid rafts at the lamellipodium of neutrophils: apparent role in calcium signaling. J Immunol 172(8):4681–5

    Google Scholar 

  • Klein JB, Rane MJ, Scherzer JA, Coxon PY, Kettritz R, Methiesen JM, Buridi A, McLeish KR (2000) Granulocyte-macrophage colony stimulating factor delays neutrophil constitutive apoptosis through phosphoinositide 3-kinase and extracellular signal regulated kinase pathways. J Immunol 164(8):4286–4291

    Article  CAS  PubMed  Google Scholar 

  • Krishnan J, Selvarajoo K, Tsuchiya M, Lee G, Choi S (2007) Toll-like receptor signal transduction. Exp Mol Med 39(4):421–438

    Article  CAS  PubMed  Google Scholar 

  • Kroemer G, Dallaporta B, Resche-Rigon M (1998) The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60:619–642

    Article  CAS  PubMed  Google Scholar 

  • Kushner EJ, MacEneaney OJ, Weil BR et al (2011) Aging is associated with a proapoptotic endothelial progenitor cell phenotype. J Vasc Res 48(5):408–414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larbi A, Douziech N, Dupuis G, Khalil A, Pelletier H, Guérard KP, Fülöp T Jr (2004a) Age-associated alterations in the recruitment of signal transduction proteins to lipid rafts in human T lymphocytes. J Leukoc Biol 75(2):373–381

    Article  CAS  PubMed  Google Scholar 

  • Larbi A, Douziech N, Khalil A, Dupuis G, Gheraïri S, Guérard P, Fülöp T Jr (2004b) Effects of Methyl-β-cyclodextrin on T lymphocytes lipid rafts with ageing. Exp Gerontol 39(4):551–558

    Google Scholar 

  • Larbi A, Douziech N, Fortin CF, Linteau A, Dupuis G, Fulop T (2005) The role of the MAPK pathway alterations in GM-CSF modulated human neutrophil apoptosis with aging. Immun Ageing 2(1):6

    Article  PubMed  PubMed Central  Google Scholar 

  • Larbi A, Dupuis G, Khalil A, Douziech N, Fortin CF, Fulop T (2006) Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging. Cell Signal 18(7): 1017–1030

    Article  CAS  PubMed  Google Scholar 

  • Larbi A, Fortin C, Dupuis G, Berrougui H, Khalil A, Fulop T (2014) Immunomodulatory role of high-density lipoproteins: impact on immunosenescence. Age 36(5):9712–9717

    Article  PubMed  PubMed Central  Google Scholar 

  • Lipschitz DA, Udupa KB, Boxer LA (1988) The role of calcium in the age-related decline of neutrophil function. Blood 71(3):659–695

    CAS  PubMed  Google Scholar 

  • Lorent JH, Levental I (2015) Structural determinants of protein partitioning into ordered membrane domains and lipid rafts. Chem Phys Lipids 192:23–32

    Article  CAS  PubMed  Google Scholar 

  • Mayer TZ, Simard FA, Cloutier A, Vardhan H, Dubois CM, McDonald PP (2013) The p38-MSK1 signaling Cascade influences cytokine production through CREB and C/EBP factors in human neutrophils. J Immunol 191(8):4299–4307

    Article  CAS  PubMed  Google Scholar 

  • Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1(2):135–145

    Article  CAS  PubMed  Google Scholar 

  • Miller EJ, Linge HM (2017) Age-related changes in immunological and physiological responses following pulmonary challenge. Int J Mol Sci 18(6):1294

    Article  PubMed Central  Google Scholar 

  • Montgomery RR, Shaw AC (2015) Paradoxical changes in innate immunity in aging: recent progress and new directions. J Leukoc Biol 98(6):937–943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moulding DA, Quayle JA, Hart CA, Edwards SW (1998) Mcl-1 expression in human neutrophils: regulation by cytokines and correlation with cell survival. Blood 92(7):2495–502

    Google Scholar 

  • Monti D, Ostan R, Borelli V, Castellani G, Franceschi C (2016) Inflammaging and human longevity in the omics era. Mech Ageing Dev 165:129

    Article  PubMed  Google Scholar 

  • Nakata Y, Tomkowicz B, Gewirtz AM, Ptasznik A (2006) Integrin inhibition through Lyn-dependent cross talk from CXCR4 chemokine receptors in normal human CD34+ marrow cells. Blood 107(11):4234–4239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Odobasic D, Kitching AR, Holdsworth SR (2016) Neutrophil-mediated regulation of innate and adaptive immunity: the role of myeloperoxidase. J Immunol Res 2016:2349817

    Article  PubMed  PubMed Central  Google Scholar 

  • Ornatowska M, Azim AC, Wang X, Christman JW, Xiao L, Joo M, Sadikot RT (2007) Functional genomics of silencing TREM-1 on TLR4 signaling in macrophages. Am J Physiol Lung Cell Mol Physiol 293(6):L1377–L1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian F, Guo X, Wang X et al (2014) Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging. Aging (Albany NY) 6(2):131–139

    Article  Google Scholar 

  • Radsak MP, Salih HR, Rammensee HG, Schild H (2004) Triggering receptor expressed on myeloid cells-1 in neutrophil inflammatory responses: differential regulation of activation and survival. J Immunol 172(8):4956–4963

    Article  CAS  PubMed  Google Scholar 

  • Rao KMK, Currie MS, Padmadabhan J, Cohen HJ (1992) Age-related alterations in actin cytoskeleton and receptor expression in human leukocytes. J Gerontol 47(2):B37–B44

    Article  CAS  PubMed  Google Scholar 

  • Read CB, Kuijper JL, Hjorth SA, Heipel MD, Tang X, Fleetwood AJ, Dantzler JL, Grell SN, Kastrup J, Wang C, Brandt CS, Hansen AJ, Wagtmann NR, Xu W, Stennicke VW (2015) Cutting edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1. J Immunol 194(4):1417–1421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rivnay B, Bergman S, Shinitzky M, Globerson A (1980) Correlations between membrane viscosity, serum cholesterol, lymphocytes activation and ageing in man. Mech Ageing Dev 12(2):119–126

    Article  CAS  PubMed  Google Scholar 

  • Ruiz-Pachecoa JA, Vivanco-Cidc H, Izaguirre-Hernándezc IY, Estrada-Garcíab I, Arriaga-Pizanod L, Chacón-Salinasb R, Fonseca-Coronadoe S, Vaughana G, Ruiz Tovara K, Rivera-Sato N, Sakamaki K, Terada N, Arai K, Miyajima A (1993) Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common beta subunit responsible for different signalling. EMBO J 12(11):4181–4189

    Article  Google Scholar 

  • Ruiz-Pacheco JA, Vivanco-Cid H, Izaguirre-Hernández IY, Estrada-García I, Arriaga-Pizano L, Chacón-Salinas R, Fonseca-Coronado S, Vaughan G, Tovar KR, Rivera-Osorio MP, Escobar-Gutiérrez A (2014) TREM-1 modulation during early stages of dengue virus infection. Immunol Lett 158(1–2):183–188

    Google Scholar 

  • Sakamoto E1, Hato F, Kato T, Sakamoto C, Akahori M, Hino M, Kitagawa S (2005) Type I and type II interferons delay human neutrophil apoptosis via activation of STAT3 and up-regulation of cellular inhibitor of apoptosis 2. J Leukoc Biol 78(1):301–9

    Google Scholar 

  • Shaw AC, Goldstein DR, Montgomery RR (2013) Age-dependent dysregulation of innate immunity. Nat Rev Immunol 13(12):875–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simard FA, Cloutier A, Ear T, Vardhan H, McDonald PP (2015) MEK-independent ERK activation in human neutrophils and its impact on functional responses. J Leukoc Biol 98(4):565–573

    Article  CAS  PubMed  Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387(6633):569–572

    Article  CAS  PubMed  Google Scholar 

  • Sitrin RG, Johnson DR, Pan PM, Harsh DM, Huang J, Petty HR, Blackwood RA (2004) Lipid rafts compartmentalization of urokinase receptor signalling in human neutrophils. Am J Respir Cell Mol Biol 30(2):233–241

    Article  CAS  PubMed  Google Scholar 

  • Shen Y, Devgan G, Darnell JE Jr, Bromberg JF (2001) Constitutively activated Stat3 protects fibroblasts from serum withdrawal and UV-induced apoptosis and antagonizes the proapoptotic effects of activated Stat1. Proc Natl Acad Sci USA 98(4):1543–8

    Google Scholar 

  • Shinitzky M (1987) Patterns of lipid changes in membranes of the aged brain. Gerontology 33(3-4):149–54

    Google Scholar 

  • Stoyanov B, Volinia S, Hanck T, Rubio I, Loubtchenkov M, Malek D, Stoyanova S, Vanhaesebroeck B, Dhand R, Nurnberg B, Gierschik P, Seedorf K, Hsuan JJ, Waterfield MD, Wetzker R (1995) Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science 269(5224):690–693

    Article  CAS  PubMed  Google Scholar 

  • Sylvain-Prevost S, Ear T, Simard FA, Fortin C, Dubois CM, Flamand N, McDonald PP (2015) Activation of TAK1 by chemotactic and growth factors, and its impact on human neutrophil signaling and functional responses. J Immunol 195(11):5393–5403

    Article  CAS  PubMed  Google Scholar 

  • Tamassia N, Le Moigne V, Calzetti F, Donini M, Gasperini S, Ear T, Cloutier A, Martinez FO, Fabbri M, Locati M, Mantovani A, McDonald PP, Cassatella M (2007) The MyD88-independent pathway is not mobilized in human neutrophils stimulated via TLR4. J Immunol 178(11):7344–7356

    Article  CAS  PubMed  Google Scholar 

  • Tortorella C, Piazzolla G, Spaccavento F, Pece S, Jirillo E, Antonaci S (1998) Spontaneous and Fas induced apoptotic cell death in aged neutrophils. J Clin Immunol 18(5):321–329

    Article  CAS  PubMed  Google Scholar 

  • Tortorella C, Stella I, Piazzolla G, Simone O, Cappiello V, Antonaci S (2004) Role of defective ERK phosphorylation in the impaired GM-CSF-induced oxidative response of neutrophils in elderly humans. Mech Ageing Dev 125(8):539–546

    Article  CAS  PubMed  Google Scholar 

  • Tortorella C, Simone O, Piazzolla G, Stella I, Cappiello V, Antonaci S (2006) Role of phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways in granulocyte macrophage–colony-stimulating factor failure to delay Fas-induced neutrophil apoptosis in elderly humans. J Gerontol A Biol Sci Med Sci 61(11):1111–1118

    Article  PubMed  Google Scholar 

  • Tortorella C, Simone O, Piazzolla G, Stella I, Antonaci S (2007) Age-related impairment of GM-CSF-induced signalling in neutrophils: role of SHP-1 and SOCS proteins. Ageing Res Rev 6(2):81–93

    Article  CAS  PubMed  Google Scholar 

  • Valayer A, Brea D, Lajoie L, Avezard L, Combes-Soia L, Labas V, Korkmaz B, Thibault G, Baranek T, Si-Tahar M (2017) Neutrophils can disarm NK cell response through cleavage of NKp46. J Leukoc Biol 101(1):253–259

    Article  CAS  PubMed  Google Scholar 

  • Watanabe S, Itoh T, Arai K (1997) Roles of JAK kinase in human GM-CSF receptor signals. Leukemia 11(S3):76–78

    PubMed  Google Scholar 

  • Zu YL, Qi J, Gilchrist A, Fernandez GA, Vazquez-Abad D, Kreutze DL, Huang CK, Sha’afi RI (1998) p38 mitogen-activated protein kinase activation is required for human neutrophil function triggered by TNF-alpha or fMLP stimulation. J Immunol 160(4):1982–1989

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We apologize to members of the scientific community whose contributions could not be cited. This work was supported by a grant-in-aid from the National Science and Engineering Research Council of Canada (No 249549), Research Center on Aging of Sherbrooke, the ImAginE Consortium, and the Canadian Institute of Health Research (No 63149).

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Authors and Affiliations

  1. Division of Geriatric Medicine, Department of Medicine, Research Center on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada

    Carl Fortin & Tamas Fulop

  2. Singapore Immunology Network (SIgN), Aging and Immunity Program, Agency for Science Technology and Research (A*STAR), Singapore, Singapore

    Anis Larbi

  3. Immunology Programme, Department of Biochemistry, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC, Canada

    Gilles Dupuis

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  1. Carl Fortin
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  2. Tamas Fulop
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  3. Anis Larbi
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  4. Gilles Dupuis
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Correspondence to Carl Fortin .

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Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, QC, Canada

    Tamas Fulop

  2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

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Fortin, C., Fulop, T., Larbi, A., Dupuis, G. (2018). Signal Transduction Changes in Human Neutrophils with Age. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_23-1

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  • DOI: https://doi.org/10.1007/978-3-319-64597-1_23-1

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