Deficient in vitro and in vivo phagocytosis of apoptotic T cells by resident murine alveolar macrophages.
Apoptotic lymphocytes are readily identified in murine lungs, both during the response to particulate Ag and in normal mice. Because apoptotic lymphocytes are seldom detected in other organs, we hypothesized that alveolar macrophages (AMphi) clear apoptotic lymphocytes poorly. To test this hypothesis, we compared in vitro phagocytosis of apoptotic thymocytes by resident AMphi and peritoneal macrophages (PMphi) from normal C57BL/6 mice. AMphi were deficient relative to PMphi both in percentage containing apoptotic thymocytes (19.1 +/- 1% vs 96 +/- 2.6% positive) and in phagocytic index (0.23 +/- 0.02 vs 4.2 +/- 0.67). This deficiency was not due to kinetic differences, was seen with six other inbred mouse strains, and was not observed using carboxylate-modified polystyrene microbeads. Annexin V blockade indicated that both Mphi types cleared apoptotic T cells by a mechanism involving phosphatidylserine expression. By contrast, neither mAb blockade of a variety of receptors (CD11b, CD29, CD51, and CD61) known to be involved in clearance of apoptotic cells, nor the tetrapeptide RGDS (arginine-glycine-aspartic acid-serine) blocked ingestion by either type of macrophage. To confirm these studies, apoptotic thymocytes were given intratracheally or i.p. to normal mice, and then AMphi or PMphi were recovered 30-240 min later. Ingestion of apoptotic thymocytes by AMphi in vivo was significantly decreased at all times. Defective ingestion of apoptotic lymphocytes may preserve AMphi capacity to produce proinflammatory cytokines in host defense, but could contribute to development of autoimmunity by failing to eliminate nucleosomes.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
B
B
Hu
J
J
Sonstein
P J
PJ
Christensen
A
A
Punturieri
J L
JL
Curtis
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D007274:Injections, Intraperitoneal; D007442:Intubation, Intratracheal; D017710:Lymphocyte Transfusion; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D017304:Annexin A5; D011971:Receptors, Immunologic