RRC ID 29284
著者 Wang Q, Imamura R, Motani K, Kushiyama H, Nagata S, Suda T.
タイトル Pyroptotic cells externalize eat-me and release find-me signals and are efficiently engulfed by macrophages.
ジャーナル Int Immunol
Abstract Pathogenic intracellular bacteria often hijack macrophages for their propagation. The infected macrophages release IL-1β and IL-18 and simultaneously commit suicide, which is called pyroptosis; both responses require caspase-1. Here, we found that pyroptotic cells induced by microbial infection were efficiently engulfed by human monocytic THP-1-cell-derived macrophages or mouse peritoneal macrophages. This engulfment was inhibited by the D89E mutant of milk fat globule (MFG) epidermal growth factor (EGF) factor 8 (MFG-E8; a phosphatidylserine-binding protein) that has been shown previously to inhibit phosphatidylserine-dependent engulfment of apoptotic cells by macrophages, suggesting that the engulfment of pyroptotic cells by macrophages was also phosphatidylserine dependent. Using a pair of cell lines that respectively exhibited pyroptosis or apoptosis after muramyl dipeptide treatment, we showed that both pyroptotic and apoptotic cells bound to a T-cell immunoglobulin and mucin domain-containing 4 (Tim4; another phosphatidylserine-binding protein)-coated plate, whereas heat-killed necrotic cells did not, indicating that phosphatidylserine was externalized in pyroptosis and apoptosis but not in accidental necrosis. Macrophages engulfed apoptotic cells most efficiently, followed by pyroptotic and then heat-killed necrotic cells. Pyroptotic cells also released a macrophage attractant(s), 'find-me' signal, whose activity was diminished by apyrase that degrades nucleoside triphosphate to nucleoside monophosphate. Heat-killed necrotic cells and pyroptotic cells released ATP much more efficiently than apoptotic cells. These results suggest that pyroptotic cells, like apoptotic cells, actively induce phagocytosis by macrophages using 'eat-me' and find-me signals. Based on these results, a possible role of coordinated induction of pyroptosis and inflammatory cytokine production is discussed.
巻・号 25(6)
ページ 363-72
公開日 2013-6-1
DOI 10.1093/intimm/dxs161
PII dxs161
PMID 23446850
MeSH Animals Cell Communication / immunology* Cell Line, Tumor Humans Macrophages / cytology Macrophages / immunology* Macrophages / microbiology* Mice Mice, Inbred C57BL Phagocytosis / immunology*
IF 3.519
引用数 37
WOS 分野 IMMUNOLOGY
リソース情報
一般微生物 JCM 1652 JCM 14847