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外体分泌的SCIMP调节了肺炎中巨细胞和中性粒细胞之间的通信

Xiaolei Pei^1,2, Li Liu^3,4, Jieru Wang^3,4

¹State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Hematopoietic Stem Cell Transplantation Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, P. R. China. peixiaolei@ihcams.ac.cn.

Nature communications

|January 23, 2024

概括

巨细胞分泌SCIMP外体,增强中性粒细胞的招募,改善急性肺损伤 (ALI) 的生存率. 这种巨-SCIMP-甲基受体 (FPR) -中性粒细胞轴对于ALI的先天免疫是至关重要的.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
肺部病理学肺部病理学

背景情况:

肺炎中病原体清除不足可能导致急性肺损伤 (ALI),原因是免疫反应过度活跃.
SLP适配器和CSK相互作用膜蛋白 (SCIMP) 在ALI期间表现出中性粒细胞化学反应活性,但其作用尚不清楚.

研究的目的:

调查巨细胞在外体内分泌的SCIMP (SCIMP^exo) 在ALI的发病过程中的作用.
阐明SCIMP影响ALI中中性粒细胞活性和存活的机制.

主要方法:

从肺炎患者的支气管洗液和血清中评估了SCIMP^exo水平.
研究了SCIMP^exo和SCIMP N-终端对小鼠模型中ALI存活率的影响.
利用外体抑制剂和甲基受体1/2 (FPR1/2) 抗剂来评估SCIMP-FPR通路.
与野生类型对照小鼠的Scimp缺陷和Fpr1/2缺陷小鼠的生存率进行比较.

主要成果:

在肺炎患者中,SCIMP^exo水平显著升高.
用SCIMP^exo或的支气管输液通过通过FPR1/2.2吸引和激活中性粒细胞来增加ALI模型的存活率.
外体抑制剂和FPR1/2抗剂在致命的ALI模型中降低了生存率.
缺乏Mcimp和Fpr1/2的小鼠的生存率较低.

结论:

巨-SCIMP-FPRs-中性粒细胞轴是ALI先天免疫反应的关键组成部分.
通过调解中性粒细胞的招募和激活,SCIMP在ALI中起着保护作用.
准SCIMP-FPR通路可能为治疗ALI提供治疗潜力.

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