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 (AM phi) clear apoptotic lymphocytes poorly. To test this hypothesis, we compared in vitro phagocytosis of apoptotic thymocytes by resident AM phi and peritoneal macrophages (PM phi) from normal C57BL/6 mice. AM phi were deficient relative to PM phi 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 phi 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 phi or PM phi were recovered 30-240 min later, Ingestion of apoptotic thymocytes by AM phi in vivo was significantly decreased at all times, Defective ingestion of apoptotic lymphocytes may preserve AM phi capacity to produce proinflammatory cytokines in host defense, but could contribute to development of autoimmunity by failing to eliminate nucleosomes.