Lipopolysaccharide inhibits macrophage phagocytosis of apoptotic neutrophils by regulating the production of tumour necrosis factor α and growth arrest-specific gene 6

P>Removal of apoptotic cells from inflammatory sites by macrophages is an important step in the resolution of inflammation. However, the effect of inflammatory modulators on phagocytic clearance of apoptotic cells remains to be clarified. In this paper, we demonstrate that lipopolysaccharide (LPS), a potent inflammatory agent, inhibits the phagocytosis of apoptotic neutrophils by mouse peritoneal macrophages. This inhibition can be attributed to both LPS-mediated induction of tumour necrosis factor (TNF-alpha) and suppression of growth arrest-specific gene 6 (Gas6) in macrophages. We found that LPS-induced TNF-alpha production inhibited phagocytic ability of macrophages in an autocrine manner. In contrast, Gas6 expression in macrophages was blocked by LPS, which also contributes to the inhibition of macrophage phagocytosis by LPS. Our data suggest that phagocytic clearance of apoptotic neutrophils by macrophages can be regulated by local pro- and anti-inflammatory factors in two opposite states.