Document Detail

Deficient in vitro and in vivo phagocytosis of apoptotic T cells by resident murine alveolar macrophages.
MedLine Citation:
PMID:  10925298     Owner:  NLM     Status:  MEDLINE    
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.
B Hu; J Sonstein; P J Christensen; A Punturieri; J L Curtis
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  165     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-14     Completed Date:  2000-09-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2124-33     Citation Subset:  AIM; IM    
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
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MeSH Terms
Annexin A5 / metabolism
Apoptosis / immunology*
Cell Movement / immunology
Cells, Cultured
Coculture Techniques
Injections, Intraperitoneal
Intubation, Intratracheal
Lymphocyte Transfusion
Macrophages, Alveolar / cytology,  immunology*,  metabolism
Macrophages, Peritoneal / cytology,  immunology,  metabolism
Mice, Inbred AKR
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Phagocytosis / immunology*
Protein Binding / immunology
Receptors, Immunologic / biosynthesis
T-Lymphocytes / cytology,  immunology*,  metabolism,  transplantation
Thymus Gland / cytology,  immunology,  metabolism,  transplantation
Grant Support
Reg. No./Substance:
0/Annexin A5; 0/Receptors, Immunologic

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