Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes

Phagocyte recognition, uptake, and nonphlogistic degradation of neutrophils and other leukocytes undergoing apoptosis promote the resolution of inflam mation. This study assessed the effects of anti-inflammatory glucocorticoid s on this leukocyte clearance mechanism. Pretreatment of "semimature" 5-day human monocyte-derived macrophages (M phi) for 24 h with methylprednisolon e, dexamethasone, and hydrocortisone, but not the nonglucocorticoid steroid s aldosterone, estradiol, and progesterone, potentiated phagocytosis of apo ptotic neutrophils, These effects were specific in that the potentiated pha gocytosis of apoptotic neutrophils was completely blocked by the glucocorti coid receptor antagonist RU38486, and glucocorticoids did not promote 5-day M phi ingestion of opsonized erythrocytes. Similar glucocorticoid-mediated potentiation was observed with 5-day M phi, uptake of alternative apoptoti c "targets" (eosinophils and Jurkat T cells) and in uptake of apoptotic neu trophils by alternative phagocytes (human glomerular mesangial cells and mu rine M phi elicited into the peritoneum or derived from bone marrow). Impor tantly, methylprednisolone-mediated enhancement of the uptake of apoptotic neutrophils did not trigger the release of the chemokines IL-8 and monocyte chemoattractant protein-1. Furthermore, longer-term potentiation by methyl prednisolone was observed in maturing human monocyte-derived M phi, with gr eater increases in 5-day M phi uptake of apoptotic cells being observed the earlier glucocorticoids were added during monocyte maturation into M phi. We conclude that potentiation of nonphlogistic clearance of apoptotic leuko cytes by phagocytes is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolu tion of inflammatory diseases.