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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Erwig, L.-P. Articles by Rees, A. J. Search for Related Content PubMed PubMed Citation Articles by Erwig, L.-P. Articles by Rees, A. J. Related Collections Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 4 (February 15), 1999: pp. 1406-1412 Previous Uptake of Apoptotic Neutrophils or Ligation of Integrin Receptors Downmodulates the Ability of Macrophages to Ingest Apoptotic Neutrophils Lars-Peter Erwig, Sharon Gordon, Garry M. Walsh, and Andrew J. Rees From the Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK. Clearance of apoptotic neutrophils (polymorphonuclear leukocyte [PMN]) by macrophages is thought to play a crucial role in resolution of acute inflammation. There is increasing evidence that ingestion of apoptotic cells modulates macrophage behavior. We therefore performed experiments to determine whether ingestion of apoptotic PMN modulated the uptake process itself. Rat bone marrow-derived macrophages (BMDM) ingested apoptotic PMN by a process that was enhanced by tumor necrosis factor (TNF) and attenuated by interferon (IFN)-, interleukin (IL)-4, and IL-10. It was inhibitable by the tetrapeptide arg-gly-gln-ser (RGDS), therefore implicating the v3/CD36/thrombospondin pathway. Interaction of apoptotic PMN with BMDM for 30 minutes, 48 hours before rechallenge reduced uptake of apoptotic PMN by 50% compared with previously unchallenged BMDM. Blocking initial uptake with RGDS abrogated the effect of preexposure. Comparable and sustained attenuation of uptake was obtained by ligating v3 with the monoclonal antibody (MoAb), F11, after a delay of more than 90 minutes, whereas MoAbs to CD25 and CD45 had no effect. Ligation of 61 and 12, integrins not previously implicated in the engulfment of apoptotic cells also decreased uptake with similar kinetics to F11. Therefore, apoptotic PMN regulate their own uptake through an integrin-dependent process, which can be reproduced by ligation of other integrins expressed by macrophages. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Graham, I. Ford, R. Morrison, R. N. Barker, M. Greaves, and L.-P. Erwig Anti-Endothelial Antibodies Interfere in Apoptotic Cell Clearance and Promote Thrombosis in Patients with Antiphospholipid Syndrome J. Immunol., February 1, 2009; 182(3): 1756 - 1762. [Abstract] [Full Text] [PDF] A. F. M. Maree, M. Komba, D. T. Finegood, and L. Edelstein-Keshet A quantitative comparison of rates of phagocytosis and digestion of apoptotic cells by macrophages from normal (BALB/c) and diabetes-prone (NOD) mice J Appl Physiol, January 1, 2008; 104(1): 157 - 169. [Abstract] [Full Text] [PDF] L.-P. Erwig and P. M. Henson Immunological Consequences of Apoptotic Cell Phagocytosis Am. J. Pathol., July 1, 2007; 171(1): 2 - 8. [Abstract] [Full Text] [PDF] M Bijl, E Reefman, G Horst, P C Limburg, and C G M Kallenberg Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement Ann Rheum Dis, January 1, 2006; 65(1): 57 - 63. [Abstract] [Full Text] [PDF] I. Jutras, A. Laplante, J. Boulais, S. Brunet, G. Thinakaran, and M. Desjardins {gamma}-Secretase Is a Functional Component of Phagosomes J. Biol. Chem., October 28, 2005; 280(43): 36310 - 36317. [Abstract] [Full Text] [PDF] J. H. Jennings, D. J. Linderman, B. Hu, J. Sonstein, and J. L. Curtis Monocytes Recruited to the Lungs of Mice during Immune Inflammation Ingest Apoptotic Cells Poorly Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 108 - 117. [Abstract] [Full Text] [PDF] A. Noguera, E. Sala, A. R. Pons, J. Iglesias, W. MacNee, and A. G.N. Agusti Expression of Adhesion Molecules During Apoptosis of Circulating Neutrophils in COPD Chest, May 1, 2004; 125(5): 1837 - 1842. [Abstract] [Full Text] [PDF] A. W. M. Minto, L.-P. Erwig, and A. J. Rees Heterogeneity of Macrophage Activation in Anti-Thy-1.1 Nephritis Am. J. Pathol., November 1, 2003; 163(5): 2033 - 2041. [Abstract] [Full Text] [PDF] M. F. Reidy and J. R. Wright Surfactant protein A enhances apoptotic cell uptake and TGF-{beta}1 release by inflammatory alveolar macrophages Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L854 - L861. [Abstract] [Full Text] [PDF] P. K. Potter, J. Cortes-Hernandez, P. Quartier, M. Botto, and M. J. Walport Lupus-Prone Mice Have an Abnormal Response to Thioglycolate and an Impaired Clearance of Apoptotic Cells J. Immunol., March 15, 2003; 170(6): 3223 - 3232. [Abstract] [Full Text] [PDF] Y. Moodley, P. Rigby, C. Bundell, S. Bunt, H. Hayashi, N. Misso, R. McAnulty, G. Laurent, A. Scaffidi, P. Thompson, et al. Macrophage Recognition and Phagocytosis of Apoptotic Fibroblasts Is Critically Dependent on Fibroblast-Derived Thrombospondin 1 and CD36 Am. J. Pathol., March 1, 2003; 162(3): 771 - 779. [Abstract] [Full Text] [PDF] B. Hu, A. Punturieri, J. Todt, J. Sonstein, T. Polak, and J. L. Curtis Recognition and phagocytosis of apoptotic T cells by resident murine tissue macrophages require multiple signal transduction events J. Leukoc. Biol., May 1, 2002; 71(5): 881 - 889. [Abstract] [Full Text] [PDF] B. Hu, J. Sonstein, P. J. Christensen, A. Punturieri, and J. L. Curtis Deficient In Vitro and In Vivo Phagocytosis of Apoptotic T Cells by Resident Murine Alveolar Macrophages J. Immunol., August 15, 2000; 165(4): 2124 - 2133. [Abstract] [Full Text] [PDF] N. Platt, H. Suzuki, T. Kodama, and S. Gordon Apoptotic Thymocyte Clearance in Scavenger Receptor Class A-Deficient Mice Is Apparently Normal J. Immunol., May 1, 2000; 164(9): 4861 - 4867. [Abstract] [Full Text] [PDF] L.-P. Erwig, K. Stewart, and A. J. Rees Macrophages from Inflamed but Not Normal Glomeruli Are Unresponsive to Anti-Inflammatory Cytokines Am. J. Pathol., January 1, 2000; 156(1): 295 - 301. [Abstract] [Full Text] [PDF] G. M. Walsh, D. W. Sexton, M. G. Blaylock, and C. M. Convery Resting and Cytokine-Stimulated Human Small Airway Epithelial Cells Recognize and Engulf Apoptotic Eosinophils Blood, October 15, 1999; 94(8): 2827 - 2835. [Abstract] [Full Text] [PDF] R. F. Thorne, J. F. Marshall, D. R. Shafren, P. G. Gibson, I. R. Hart, and G. F. Burns The Integrins alpha 3beta 1 and alpha 6beta 1 Physically and Functionally Associate with CD36 in Human Melanoma Cells. REQUIREMENT FOR THE EXTRACELLULAR DOMAIN OF CD36 J. Biol. Chem., November 3, 2000; 275(45): 35264 - 35275. [Abstract] [Full Text] [PDF]

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