巨噬细胞
肺泡巨噬细胞
整合素αM
过继性细胞移植
免疫学
刺
炎症
传出细胞增多
医学
鞘氨醇
癌症研究
化学
免疫系统
受体
内科学
T细胞
生物化学
体外
航空航天工程
工程类
作者
Jagdish C. Joshi,Brijendra Kumar Joshi,Ian Rochford,Sheikh Rayees,Zahid Akhter,Sukriti Baweja,Koteshwara Rao Chava,Mohammad Tauseef,Hazem Abdelkarim,Viswanathan Natarajan,Vadim Gaponenko,Dolly Mehta
出处
期刊:Cell Reports
[Elsevier]
日期:2020-03-01
卷期号:30 (12): 4096-4109.e5
被引量:32
标识
DOI:10.1016/j.celrep.2020.02.112
摘要
Acute lung injury (ALI) is a lethal inflammatory lung disorder whose incidence is on the rise. Alveolar macrophages normally act to resolve inflammation, but when dysregulated they can provoke ALI. We demonstrate that monocyte-derived macrophages (CD11b+ macrophages) recruited into the airspace upregulate the anti-inflammatory function of alveolar macrophages by suppressing their stimulator of type 1 interferon gene (STING) signaling. Depletion of CD11b+ macrophages in mice (macrophagedep mice) after endotoxin or after Pseudomonas aeruginosa causes expansion of the inflammatory alveolar macrophage population, leading to neutrophil accumulation, irreversible loss of lung vascular barrier function, and lethality. We show that CD11b+ macrophages suppress alveolar macrophage-STING signaling via sphingosine kinase-2 (SPHK2) generation of sphingosine-1-phosphate (S1P). Thus, adoptive transfer of wild-type (WT) or STING−/−, but not SPHK2−/−, CD11b monocytes from murine bone marrow into injured macrophagedep mice rescue anti-inflammatory alveolar macrophages and reverse lung vascular injury. SPHK2-induced S1P generation in CD11b+ macrophages has the potential to educate alveolar macrophages to resolve ALI.
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