Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor.
Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor.
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DOI：
10.1084/jem.20120096
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发表时间：
2012-07-30
期刊：
影响因子：
--
通讯作者：
Shibuya A
中科院分区：
文献类型：
--
作者：
Nakahashi-Oda C;Tahara-Hanaoka S;Shoji M;Okoshi Y;Nakano-Yokomizo T;Ohkohchi N;Yasui T;Kikutani H;Honda S;Shibuya K;Nagata S;Shibuya A
盲肠结扎和穿刺后，肥大细胞上缺乏磷脂酰丝氨酸受体CD 300 a的小鼠显示更多的中性粒细胞募集到腹腔，改善细菌清除，延长生存期。当细胞发生凋亡时，磷脂酰丝氨酸（PS）暴露在质膜的外小叶上。PS作为一种“吃我”信号，指导表达PS受体的吞噬细胞吞噬凋亡细胞。我们最近报道，免疫受体CD 300 a，这是表达在骨髓细胞，是一个PS受体。我们发现，CD 300 a并不促进凋亡细胞的巨噬细胞吞噬。相反，CD 300 a在肥大细胞中传递抑制信号以抑制LPS诱导的炎性细胞因子和趋化因子的产生。盲肠结扎和穿孔（CLP）后，当大量的细胞在腹膜腔中进行凋亡，CD 300 α缺陷的腹膜肥大细胞产生更多的趋化因子，并招募更多的中性粒细胞比野生型（WT）肥大细胞。结果，CD 300 a缺陷型小鼠表现出增加的中性粒细胞募集和腹膜腔中改善的细菌清除，并且存活时间长于WT小鼠。CD 300 a-PS相互作用的抗体阻断改善了细菌清除并延长了经受CLP的WT小鼠的存活。这些结果表明，CD 300 a是一种非吞噬PS受体，调节肥大细胞对微生物感染的炎症反应。
After cecal ligation and puncture, mice lacking the phosphatidylserine receptor CD300a on mast cells show more neutrophil recruitment to the peritoneal cavity, improved bacterial clearance, and extended survival. When a cell undergoes apoptosis, phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. PS acts as an “eat-me” signal to direct phagocytes expressing PS receptors to engulf the apoptotic cell. We recently reported that the immunoreceptor CD300a, which is expressed on myeloid cells, is a PS receptor. We show that CD300a does not facilitate macrophage phagocytosis of apoptotic cells. Instead, CD300a delivers an inhibitory signal in mast cells to suppress production of LPS-induced inflammatory cytokines and chemokines. After cecal ligation and puncture (CLP), when a large number of cells undergo apoptosis in the peritoneal cavity, CD300a-deficient peritoneal mast cells produced more chemoattractant and recruited more neutrophils than did wild-type (WT) mast cells. As a result, CD300a-deficient mice showed increased neutrophil recruitment and improved bacterial clearance in the peritoneal cavity, and survived longer than WT mice. Antibody blockade of CD300a–PS interactions improved bacterial clearance and extended survival of WT mice subjected to CLP. These results indicated that CD300a is a nonphagocytic PS receptor that regulates mast cell inflammatory responses to microbial infections.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
DOI：
10.1038/nri2782
发表时间：
2010-06
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.4
作者：
Chung, DH;Humphrey, MB;Daws, MR
通讯作者：
Daws, MR
影响因子：
6
作者：
Grimbaldeston, MA;Chen, CC;Galli, SJ
通讯作者：
Galli, SJ
影响因子：
56.9
作者：
Hanayama, R;Tanaka, M;Nagata, S
通讯作者：
Nagata, S