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Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109; and
Pulmonary and Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Medical Center, Ann Arbor, MI 48105
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 (AM
) clear apoptotic
lymphocytes poorly. To test this hypothesis, we compared in vitro
phagocytosis of apoptotic thymocytes by resident AM and peritoneal
macrophages (PM) from normal C57BL/6 mice. AM were deficient
relative to PM 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 M 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 AM or PM were recovered 30–240 min later.
Ingestion of apoptotic thymocytes by AM in vivo was significantly
decreased at all times. Defective ingestion of apoptotic lymphocytes
may preserve AM capacity to produce proinflammatory cytokines in
host defense, but could contribute to development of autoimmunity by
failing to eliminate nucleosomes.
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