Nonphlogistic clearance of late apoptotic neutrophils by macrophages: efficient phagocytosis independent of β2 integrins

Y Ren, L Stuart, FP Lindberg… - The Journal of …, 2001 - journals.aai.org
Y Ren, L Stuart, FP Lindberg, AR Rosenkranz, Y Chen, TN Mayadas, J Savill
The Journal of Immunology, 2001journals.aai.org
Neutrophils undergo constitutive death by apoptosis, leading to safe nonphlogistic
phagocytosis and clearance by macrophages. Recent work has shown that before
secondary necrosis, neutrophils exhibiting classical features of apoptosis can progress to a
morphologically defined late apoptotic state. However, whether such neutrophils could be
safely cleared was unknown. We now report that human late apoptotic neutrophils could be
purified from cultured neutrophil populations undergoing constitutive death and were …
Abstract
Neutrophils undergo constitutive death by apoptosis, leading to safe nonphlogistic phagocytosis and clearance by macrophages. Recent work has shown that before secondary necrosis, neutrophils exhibiting classical features of apoptosis can progress to a morphologically defined late apoptotic state. However, whether such neutrophils could be safely cleared was unknown. We now report that human late apoptotic neutrophils could be purified from cultured neutrophil populations undergoing constitutive death and were subsequently ingested by human monocyte-derived macrophages by serum-independent mechanisms that did not trigger the release of IL-8 or TNF-α. Such ingestion was specifically inhibited by Abs to thrombospondin-1 and the α v β 3 vitronectin receptor. Murine bone marrow-derived macrophage phagocytosis of late and early apoptotic neutrophils occurred by similar mechanisms, proceeding with the same efficiency as that observed for wild-type controls when macrophages from α m−/− or β 2−/− mice were used. We conclude that specific nonphlogistic, β 2 integrin-independent mechanisms involving thrombospondin-1 and α v β 3 allow macrophages to ingest late apoptotic neutrophils without eliciting inflammatory cytokine secretion.
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