title: Glucocorticoids promote nonphlogistic phagocytosis of apoptotic leukocytes.
abstract: Phagocyte recognition, uptake, and nonphlogistic degradation of neutrophils and other leukocytes undergoing apoptosis promote the resolution of inflammation. This study assessed the effects of anti-inflammatory glucocorticoids on this leukocyte clearance mechanism. Pretreatment of "semimature" 5-day human monocyte-derived macrophages (M phi) for 24 h with methylprednisolone, dexamethasone, and hydrocortisone, but not the nonglucocorticoid steroids aldosterone, estradiol, and progesterone, potentiated phagocytosis of apoptotic neutrophils. These effects were specific in that the potentiated phagocytosis of apoptotic neutrophils was completely blocked by the glucocorticoid 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 apoptotic "targets" (eosinophils and Jurkat T cells) and in uptake of apoptotic neutrophils by alternative phagocytes (human glomerular mesangial cells and murine M phi elicited into the peritoneum or derived from bone marrow). Importantly, 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 methylprednisolone was observed in maturing human monocyte-derived M phi, with greater 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 leukocytes by phagocytes is a hitherto unrecognized property of glucocorticoids that has potential implications for therapies aimed at promoting the resolution of inflammatory diseases.
authors: Division of Renal and Inflammatory Disease, School of Medical and Surgical Sciences, University Hospital, Nottingham, United Kingdom.
authors: Y
authors: Y
authors: Liu
authors: J M
authors: JM
authors: Cousin
authors: J
authors: J
authors: Hughes
authors: J
authors: J
authors: Van Damme
authors: J R
authors: JR
authors: Seckl
authors: C
authors: C
authors: Haslett
authors: I
authors: I
authors: Dransfield
authors: J
authors: J
authors: Savill
authors: A G
authors: AG
authors: Rossi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003513:Cycloheximide