Advertisement

Fate of macrophages once having ingested apoptotic cells: Lymphatic clearance or in situ apoptosis?

  • Geoffrey J. Bellingan
  • Geoffrey J. Laurent
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Neutrophil and macrophage kinetics at the inflamed site differ markedly [1, 2]. Unlike neutrophils, many organs and tissues have a population of resident macrophages, hence these cells have a different baseline at the outset of inflammation. Resident macrophages are a key population in the initiation of local inflammation [3]. Neutrophils influx rapidly early in the acute inflammatory event, while resident tissue macrophages may actually decline in numbers due to a process known as the macrophage disappearance reaction (MDR) [4]. Like neutrophils, inflammatory monocytes migrate in from the blood stream, although this lags somewhat behind the insurgence of neutrophils. These monocytes mature locally into inflammatory macrophages, although their activation state may alter over the course of the inflammatory process [5, 6]. Neutrophil numbers peak earlier than macrophages. Their decline can be due to necrosis, apoptosis and subsequent phagocytosis, or progressing to secondary necrosis if phagocytosis of apoptotic cells fails [7]. Neutrophils may be able to efflux away from the inflamed site, for example back into the blood stream, or, with pulmonary inflammation for example, they can migrate into the airway lumen [8]–[10]. It appears, however, that their main fate is to undergo apoptosis locally as shown in a number of models and in vivo settings [7, 11]. In normally resolving inflammation, macrophages phagocytose the apoptotic neutrophils and their numbers then decline allowing the tissue to return to normal structure and function [12]–[14]. This chapter examines macrophage clearance in the resolution of inflammation.

Keywords

Nitric Oxide Apoptotic Cell Drain Lymph Node Resident Macrophage Apoptotic Neutrophil 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Melnicoff MJ, Horan PK, Morahan PS (1989) Kinetics of changes in peritoneal cell populations following acute inflammation. Cell Immunol 118: 178–191PubMedCrossRefGoogle Scholar
  2. 2.
    Bellingan G (1999) Inflammatory cell activation in sepsis. Br Med Bull 55: 12–29PubMedCrossRefGoogle Scholar
  3. 3.
    Cailhier JF, Partolina M, Vuthoori S, Wu S, Ko K, Watson S, Savill J, Hughes J, Lang RA (2005) Conditional macrophage ablation demonstrates that resident macrophages initiate acute peritoneal inflammation. J Immunol 174: 2336–2342PubMedGoogle Scholar
  4. 4.
    Barth MW, Hendrzak JA, Melnicoff MJ, Morahan PS (1995) Review of the macrophage disappearance reaction. J Leukoc Biol 57: 361–367PubMedGoogle Scholar
  5. 5.
    Riches DW (1995) Signalling heterogeneity as a contributing factor in macrophage functional diversity. Semin Cell Biol 6: 377–384PubMedCrossRefGoogle Scholar
  6. 6.
    Porcheray F, Viaud S, Rimaniol AC, Leone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G (2005) Macrophage activation switching: An asset for the resolution of inflammation. Clin Exp Immunol 142: 481–489PubMedGoogle Scholar
  7. 7.
    Brazil TJ, Dagleish MP, McGorum BC, Dixon PM, Haslett C, Chilvers ER (2005) Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation. Clin Exp Allergy 35: 854–865PubMedCrossRefGoogle Scholar
  8. 8.
    Rydell-Tormanen K, Uller L, Erjefalt JS (2006) Direct evidence of secondary necrosis of neutrophils during intense lung inflammation. Eur Respir J 28: 268–274PubMedCrossRefGoogle Scholar
  9. 9.
    Hughes J, Johnson RJ, Mooney A, Hugo C, Gordon K, Savill J (1997) Neutrophil fate in experimental glomerular capillary injury in the rat. Emigration exceeds in situ clearance by apoptosis. Am J Pathol 150: 223–234Google Scholar
  10. 10.
    Erjefalt J (2005) Transepithelial migration, necrosis and apoptosis as silent and proinflammatory fates of airway granulocytes. Curr Drug Targets Inflamm Allergy 4: 425–431PubMedCrossRefGoogle Scholar
  11. 11.
    Rysanek D, Sladek Z (2006) The image of exocytosis during neutrophils and macrophages phagocytic activities in inflammation of mammary gland triggered by experimental Staphylococcus aureus infection. Anat Histol Embryol 35: 171–177PubMedCrossRefGoogle Scholar
  12. 12.
    Haslett C (1999) Granulocyte apoptosis and its role in the resolution and control of lung inflammation. Am J Respir Crit Care Med 160: S5–11PubMedGoogle Scholar
  13. 13.
    Savill JS, Wyllie AH, Henson JE, Walport MJ, Henson PM, Haslett C (1989) Macrophage phagocytosis of aging PMNs in inflammation. Programmed cell death in the PMN leads to its recognition by macrophages. J Clin Invest 83: 865–875PubMedCrossRefGoogle Scholar
  14. 14.
    Savill J, Hogg N, Ren Y, Haslett C (1992) Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of PMNs undergoing apoptosis. J Clin Invest 90: 1513–1522PubMedCrossRefGoogle Scholar
  15. 15.
    Mangan DF, Wahl SM (1991) Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines. J Immunol 147: 3408–3412PubMedGoogle Scholar
  16. 16.
    Perera LP, Waldmann TA (1998) Activation of human monocytes induces differential resistance to apoptosis with rapid down regulation of caspase-8/FLICE. Proc Natl Acad Sci USA 95: 14308–14313PubMedCrossRefGoogle Scholar
  17. 17.
    Perlman H, Pagliari LJ, Georganas C, Mano T, Walsh K, Pope RM (1999) FLICEinhibitory protein expression during macrophage differentiation confers resistance to Fas-mediated apoptosis. J Exp Med 190: 1679–1688PubMedCrossRefGoogle Scholar
  18. 18.
    Kiener PA, Davis PM, Starling GC, Mehlin C, Klebanoff SJ, Ledbetter JA, Liles WC (1997) Differential induction of apoptosis by Fas-Fas ligand interactions in human monocytes and macrophages. J Exp Med 185: 1511–1516PubMedCrossRefGoogle Scholar
  19. 19.
    Munn DH, Beall AC, Song D, Wrenn RW, Throckmorton DC (1995) Activationinduced apoptosis in human macrophages: developmental regulation of a novel cell death pathway by macrophage colony-stimulating factor and interferon. J Exp Med 181: 127-136Google Scholar
  20. 20.
    Lan HY, Nikolic-Paterson DJ, Atkins RC (1993) Trafficking of inflammatory macrophages from the kidney to draining lymph nodes during experimental glomerulonephritis. Clin Exp Immunol 92: 336–341PubMedCrossRefGoogle Scholar
  21. 21.
    Bellingan GJ, Caldwell H, Howie SE Dransfield I, Haslett C (1996) In vivo fate of the inflammatory macrophage during the resolution of inflammation: Inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J Immunol 157: 2577–2585PubMedGoogle Scholar
  22. 22.
    Harmsen AG, Muggenburg BA, Snipes MB, Bice DE (1985) The role of macrophages in particle translocation from lungs to lymph nodes. Science 230: 1277–1280PubMedCrossRefGoogle Scholar
  23. 23.
    Bellingan GJ, Xu P, Cooksley H, Cauldwell H, Shock A, Bottoms S, Haslett C, Mutsaers SE, Laurent GJ (2002) Adhesion molecule-dependent mechanisms regulate the rate of macrophage clearance during the resolution of peritoneal inflammation. J Exp Med 196: 1515–1521PubMedCrossRefGoogle Scholar
  24. 24.
    Grage-Griebenow E, Durrbaum-Landmann I, Pryjma J, Loppnow H, Flad HD, Ernst M (1998) Apoptosis in monocytes. Eur Cytokine Netw 9: 699–700PubMedGoogle Scholar
  25. 25.
    Malyshev IY, Shnyra A (2003) Controlled modulation of inflammatory, stress and apoptotic responses in macrophages. Curr Drug Targets Immune Endocr Metab Disord 3: 1–22CrossRefGoogle Scholar
  26. 26.
    Hilbi H, Zychlinsky A, Sansonetti PJ (1997) Macrophage apoptosis in microbial infections. Parasitology 115(Suppl): S79–87PubMedCrossRefGoogle Scholar
  27. 27.
    Marriott HM, Bingle CD, Read RC, Braley KE, Kroemer G, Hellewell PG, Craig RW, Whyte MK, Dockrell DH (2005) Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance. J Clin Invest 115: 359–368PubMedGoogle Scholar
  28. 28.
    Komuro I, Yasuda T, Iwamoto A, Akagawa KS (2005) Catalase plays a critical role in the CSF-independent survival of human macrophages via regulation of the expression of BCL-2 family. J Biol Chem 280: 41137–41145PubMedCrossRefGoogle Scholar
  29. 29.
    Yoshioka Y, Kitao T, Kishino T, Yamamuro A, Maeda S (2006) Nitric oxide protects macrophages from hydrogen peroxide-induced apoptosis by inducing the formation of catalase. J Immunol 176: 4675–4681PubMedGoogle Scholar
  30. 30.
    Ferret PJ, Soum E, Negre O, Fradelizi D (2002) Auto-protective redox buffering systems in stimulated macrophages. BMC Immunol 3: 3PubMedCrossRefGoogle Scholar
  31. 31.
    Himes SR, Sester DP, Ravasi T, Cronau SL, Sasmono T, Hume DA (2006) The JNK are important for development and survival of macrophages. J Immunol 176: 2219–2228PubMedGoogle Scholar
  32. 32.
    Fayyazi A, Eichmeyer B, Soruri A, Schweyer S, Herms J, Schwarz P, Radzun HJ (2000) Apoptosis of macrophages and T cells in tuberculosis associated caseous necrosis. J Pathol 191: 417–425PubMedCrossRefGoogle Scholar
  33. 33.
    Tyner JW, Uchida O, Kajiwara N, Kim EY, Patel AC, O’Sullivan MP, Walter MJ, Schwendener RA, Cook DN, Danoff TM, Holtzman MJ (2005) CCL5-CCR5 interaction provides antiapoptotic signals for macrophage survival during viral infection. Nat Med 11: 1180–1187PubMedCrossRefGoogle Scholar
  34. 34.
    Francois S, El Benna J, Dang PM, Pedruzzi E, Gougerot-Pocidalo MA, Elbim C (2005) Inhibition of neutrophil apoptosis by TLR agonists in whole blood: Involvement of the phosphoinositide 3-kinase/Akt and NF-kappaB signaling pathways, leading to increased levels of Mcl-1, A1, and phosphorylated Bad. J Immunol 174: 3633–3642PubMedGoogle Scholar
  35. 35.
    Zychlinsky A, Prevost MC, Sansonetti PJ (1992) Shigella flexneri induces apoptosis in infected macrophages. Nature 358: 167–169PubMedCrossRefGoogle Scholar
  36. 36.
    Hueffer K, Galan JE (2004) Salmonella-induced macrophage death: Multiple mechanisms, different outcomes. Cell Microbiol 6: 1019–1025PubMedCrossRefGoogle Scholar
  37. 37.
    Hsu LC, Park JM, Zhang K, Luo JL, Maeda S, Kaufman RJ, Eckmann L, Guiney DG, Karin M (2004) The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428: 341–345PubMedCrossRefGoogle Scholar
  38. 38.
    Zauberman A, Cohen S, Mamroud E, Flashner Y, Tidhar A, Ber R, Elhanany E, Shafferman A, Velan B (2006) Interaction of Yersinia pestis with macrophages: Limitations in YopJ-dependent apoptosis. Infect Immun 74: 3239–3250PubMedCrossRefGoogle Scholar
  39. 39.
    Rios-Barrera VA, Campos-Pena V, Aguilar-Leon D, Lascurain LR, Meraz-Rios MA, Moreno J, Figueroa-Granados V, Hernandez-Pando R (2006) Macrophage and T lymphocyte apoptosis during experimental pulmonary tuberculosis: Their relationship to mycobacterial virulence. Eur J Immunol 36: 345–353PubMedCrossRefGoogle Scholar
  40. 40.
    Lee J, Remold HG, Ieong MH, Kornfeld H (2006) Macrophage apoptosis in response to high intracellular burden of Mycobacterium tuberculosis is mediated by a novel caspas-eindependent pathway. J Immunol 176: 4267–4274PubMedGoogle Scholar
  41. 41.
    Ali F, Lee ME, Iannelli F, Pozzi G, Mitchell TJ, Read RC, Dockrell DH (2003) Streptococcus pneumoniae-associated human macrophage apoptosis after bacterial internalization via complement and Fcgamma receptors correlates with intracellular bacterial load. J Infect Dis 188: 1119–1131PubMedCrossRefGoogle Scholar
  42. 42.
    Chang JH, Kim SK, Choi IH, Lee SK, Morio T, Chang EJ (2006) Apoptosis of macrophages induced by Trichomonas vaginalis through the phosphorylation of p38 mitogen-activated protein kinase that locates at downstream of mitochondria-dependent caspase activation. Int J Biochem Cell Biol 38: 638–647PubMedCrossRefGoogle Scholar
  43. 43.
    Lasbury ME, Durant PJ, Ray CA, Tschang D, Schwendener R, Lee CH (2006) Suppression of alveolar macrophage apoptosis prolongs survival of rats and mice with pneumocystis pneumonia. J Immunol 176: 6443–6453PubMedGoogle Scholar
  44. 44.
    Marriott H, Ali F, Read, RC, Mitchell, TJ, Whyte MKB, Dockrell DH (2004) Nitric oxide levels regulate macrophage commitment to apoptosis or necrosis during pneumococcal infection. FASEB J 18: 1126–1128PubMedGoogle Scholar
  45. 45.
    Hu B, Sonstein J, Christensen PJ, Punturieri A, Curtis JL (2000) Deficient in vitro and in vivo phagocytosis of apoptotic T cells by resident murine alveolar macrophages. J Immunol 165: 2124–2133PubMedGoogle Scholar
  46. 46.
    Jennings JH, Linderman DJ, Hu B, Sonstein J, Curtis JL (2005) Monocytes recruited to the lungs of mice during immune inflammation ingest apoptotic cells poorly. Am J Respir Cell Mol Biol 32: 108–117PubMedCrossRefGoogle Scholar
  47. 47.
    Lake FR, Noble PW, Henson PM, Riches DW (1994) Functional switching of macrophage responses to tumor necrosis factor-alpha (TNF alpha) by interferons. Implications for the pleiotropic activities of TNF alpha. J Clin Invest 93: 1661–1669PubMedCrossRefGoogle Scholar
  48. 48.
    Albina JE, Cui S, Mateo RB, Reichner JS (1993) Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J Immunol 150: 5080–5085PubMedGoogle Scholar
  49. 49.
    Hortelano S, Castrillo A, Alvarez AM, Bosca L (2000) Contribution of cyclopentenone prostaglandins to the resolution of inflammation through the potentiation of apoptosis in activated macrophages. J Immunol 165: 6525–6531PubMedGoogle Scholar
  50. 50.
    Wei J, Sun Z, Chen Q, Gu J (2006) Serum deprivation induced apoptosis in macrophage is mediated by autocrine secretion of type I IFNs. Apoptosis 11: 545–554PubMedCrossRefGoogle Scholar
  51. 51.
    Hohlbaum AM, Gregory MS, Ju ST, Marshak-Rothstein A (2001) Fas ligand engagement of resident peritoneal macrophages in vivo induces apoptosis and the production of neutrophil chemotactic factors. J Immunol 167: 6217–6224PubMedGoogle Scholar
  52. 52.
    Gilroy DW, Colville-Nash PR, McMaster S, Sawatzky DA, Willoughby DA, Lawrence T (2003) Inducible cyclooxygenase-derived 15-deoxy(Delta)12-14PGJ2 brings about acute inflammatory resolution in rat pleurisy by inducing neutrophil and macrophage apoptosis. FASEB J 17: 2269–2271PubMedGoogle Scholar
  53. 53.
    Johnson JL, Baker AH, Oka K, Chan L, Newby AC, Jackson CL, George SJ (2006) Suppression of atherosclerotic plaque progression and instability by tissue inhibitor of metalloproteinase-2: Involvement of macrophage migration and apoptosis. Circulation 113: 2435–2444PubMedCrossRefGoogle Scholar
  54. 54.
    Tunbridge AJ, Stevanin TM, Lee M, Marriott HM, Moir JW, Read RC, Dockrell DH (2006) Inhibition of macrophage apoptosis by Neisseria meningitidis requires nitric oxide detoxification mechanisms. Infect Immun 74: 729–733PubMedCrossRefGoogle Scholar
  55. 55.
    Gross A, Terraza A, Ouahrani-Bettache S, Liautard JP, Dornand J (2000) In vitro Brucella suis infection prevents the programmed cell death of human monocytic cells. Infect Immun 68: 342–351PubMedCrossRefGoogle Scholar
  56. 56.
    Lin H, Zhang XM, Chen C, Chen BD (2000) Apoptosis of Mo7e leukemia cells is associated with the cleavage of Bcl-2 into a shortened fragment that is not functional for heterodimerization with Bcl-2 and Bax. Exp Cell Res 261: 180–186PubMedCrossRefGoogle Scholar
  57. 57.
    Mogga SJ, Mustafa T, Sviland L, Nilsen R (2002) Increased Bcl-2 and reduced Bax expression in infected macrophages in slowly progressive primary murine Mycobacterium tuberculosis infection. Scand J Immunol 56: 383–391PubMedCrossRefGoogle Scholar
  58. 58.
    Rosen H, Gordon S (1990) Adoptive transfer of fluorescence-labeled cells shows that resident peritoneal macrophages are able to migrate into specialized lymphoid organs and inflammatory sites in the mouse. Eur J Immunol 20: 1251–1258PubMedCrossRefGoogle Scholar
  59. 59.
    Cao C, Lawrence DA, Strickland DK, Zhang L (2005) A specific role of integrin Mac-1 in accelerated macrophage efflux to the lymphatics. Blood 106: 3234–3241PubMedCrossRefGoogle Scholar
  60. 60.
    Hotchkiss RS, Chang KC, Grayson MH, Tinsley KW, Dunne BS, Davis CG, Osborne DF, Karl IE (2003) Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis. Proc Natl Acad Sci USA 100: 6724–6729PubMedCrossRefGoogle Scholar
  61. 61.
    Huynh ML, Fadok VA, Henson PM (2002) Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest 109: 41–50PubMedGoogle Scholar
  62. 62.
    Bellingan G, Bottoms S, Xu P, Shock T, Laurent G (2004) Apoptotic cells promote inflammatory macrophage clearance through a β1 integrin dependent mechanism. Am J Respir Crit Care Med May 25: A502Google Scholar
  63. 63.
    Molloy A, Laochumroonvorapong P, Kaplan G (2004) Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guerin. J Exp Med 180: 1499–1509CrossRefGoogle Scholar
  64. 64.
    MacPhee PJ, Schmidt EE Groom AC (1992) Evidence for Kuppfer cell migration along liver sinusoids from high resolution in vivo microscopy. Am J Physiol 263: G17–23PubMedGoogle Scholar
  65. 65.
    Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, Van Rooijen N, Takenaka H, D’Amore PA, Stein-Streilein J, Losordo DW, Streilein JW (2005) Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-ositive macrophages. J Clin Invest 115: 2363–2372PubMedCrossRefGoogle Scholar
  66. 66.
    Baluk P, Tammela T, Ator E, Lyubynska N, Achen MG, Hicklin DJ, Jeltsch M, Petrova TV, Pytowski B, Stacker SA et al (2005) Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J Clin Invest 115: 247–257PubMedGoogle Scholar
  67. 67.
    Debes GF, Arnold CN, Young AJ, Krautwald S, Lipp M, Hay JB, Butcher EC (2004) Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues Nat Immunol 6: 889–894CrossRefGoogle Scholar
  68. 68.
    Hirao M, Onai N, Hiroishi K, Watkins SC, Matsushima K, Robbins PD, Lotze MT, Tahara H (2000) CC chemokine receptor-7 on dendritic cells is induced after interaction with apoptotic tumor cells: Critical role in migration from the tumor site to draining lymph nodes. Cancer Res 60: 2209–2217PubMedGoogle Scholar
  69. 69.
    Stuart LM, Lucas M, Simpson C, Lamb J, Savill J, Lacy-Hulbert A (2002) Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation. J Immunol 168: 1627–1635PubMedGoogle Scholar
  70. 70.
    Chung EY, Kim SJ, Ma XJ (2006) Regulation of cytokine production during phagocytosis of apoptotic cells. Cell Res 16: 154–161PubMedCrossRefGoogle Scholar
  71. 71.
    van Vugt E, Arkema JM, Verdaasdonk MA, Beelen RH, Kamperdijk EW (1991) Morphological and functional characteristics of rat steady state peritoneal dendritic cells. Immunobiology 184: 14–24PubMedGoogle Scholar
  72. 72.
    Jackson DG (2004) Biology of the lymphatic marker LYVE-1 and applications in research into lymphatic trafficking and lymphangiogenesis. APMIS 112: 526–538PubMedCrossRefGoogle Scholar
  73. 73.
    O’Brien BA, Geng X, Orteu CH, Huang Y, Ghoreishi M, Zhang Y, Bush JA, Li G, Finegood DT, Dutz JP (2006) A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD mouse. J Autoimmun 26: 104–115PubMedCrossRefGoogle Scholar
  74. 74.
    Reville K, Crean JK, Vivers S, Dransfield I, Godson C (2006) Lipoxin A4 redistributes myosin IIA and Cdc42 in macrophages: implications for phagocytosis of apoptotic leukocytes J Immunol 176: 1878–1888PubMedGoogle Scholar
  75. 75.
    Amano H, Morimoto K, Senba M, Wang H, Ishida Y, Kumatori A, Yoshimine H, Oishi K, Mukaida N, Nagatake T (2004) Essential contribution of monocyte chemoattractant protein-1/C-C chemokine ligand-2 to resolution and repair processes in acute bacterial pneumonia. J Immunol 172: 398–409PubMedGoogle Scholar
  76. 76.
    Kirkham PA, Spooner G, Rahman I, Rossi AG (2004) Macrophage phagocytosis of apoptotic neutrophils is compromised by matrix proteins modified by cigarette smoke and lipid peroxidation products. Biochem Biophys Res Commun 318: 32–37PubMedCrossRefGoogle Scholar
  77. 77.
    Asada K, Sasaki S, Suda T, Chida K, Nakamura H (2004) Anti-inflammatory roles of peroxisome proliferator-activated receptor gamma in human alveolar macrophages. Am J Respir Crit Care Med 169: 195–200PubMedCrossRefGoogle Scholar
  78. 78.
    Liu Y, Cousin JM, Hughes J, Van Damme J, Seckl JR, Haslett C, Dransfield I, Savill J, Rossi AG (1999) Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes. J Immunol 162: 3639–3646PubMedGoogle Scholar
  79. 79.
    Heasman SJ, Giles KM, Rossi AG, Allen JE, Haslett C, Dransfield I (2004) Interferon gamma suppresses glucocorticoid augmentation of macrophage clearance of apoptotic cells. Eur J Immunol 34: 1752–1761PubMedCrossRefGoogle Scholar
  80. 80.
    Erwig LP, Gordon S, Walsh GM, Rees AJ (1999) Previous uptake of apoptotic PMNs or ligation of integrin receptors downmodulates the ability of macrophages to ingest apoptotic PMNs. Blood 93: 1406–1412PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Geoffrey J. Bellingan
    • 1
  • Geoffrey J. Laurent
    • 1
  1. 1.Centre for Respiratory ResearchUniversity College London, Rayne InstituteLondonUK

Personalised recommendations