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Blood:L-选择素脱落对肺内细菌清除-整合素-外-内信号通路的调控

2019-08-02 MedSci MedSci原创

革兰氏阴性菌引起的肺炎是一种常见的严重疾病,具有较高的发病率和死亡率。清除致病菌依赖于中性粒细胞的募集和功能。近期,研究发现黏附分子L-选择素参与中性粒细胞整合素活化(由内而外型信号传导)。但L-选择素参与宿主防御肺炎克雷伯菌引起的肺部炎症的分子机制尚不明确。

中心点:

L-选择素可增强整合素的外-内信号,对于宿主防御和肺炎支原体引起的肺炎中的细菌清除至关重要

IRhom2依赖的ADAM17激活可导致L-选择素脱落,并可放大中性粒细胞的效应功能

摘要:

革兰氏阴性菌引起的肺炎是一种常见的严重疾病,具有较高的发病率和死亡率。清除致病菌依赖于中性粒细胞的募集和功能。近期,研究发现黏附分子L-选择素参与中性粒细胞整合素活化(由内而外型信号传导)。但L-选择素参与宿主防御肺炎克雷伯菌引起的肺部炎症的分子机制尚不明确。

因此,Cappenberg等人对此进行深入研究,结果发现,与野生型(WT)对照组相比,L-选择素缺乏的小鼠更容易发生肺部感染。在机制上,L-选择素切割从中性粒细胞表面触发的整合素参与招募中性粒细胞进入肺和细菌清除。

在整合素连接的下游,金属蛋白酶ADAM17通过IRhom2依赖的方式将中性粒细胞表面的L-选择素释放出去。L-选择素裂解可增强整合素介导的外-内信号转导,进而增强中性粒细胞的效应功能。

综上所述,本研究揭示了中性粒细胞中的一种新的调节机制;在肺炎克雷伯杆菌诱导的肺部炎症过程中,L-选择素对整合素所触发的免疫反应的介导作用。

原始出处:

Anika Cappenberg, et al.L-selectin shedding affects bacterial clearance in the lung - a new regulatory pathway for integrin-outside-in signaling.http://www.bloodjournal.org/content/early/2019/07/31/blood.2019001185

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