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Role of Mac-1 integrin in generation of extracellular vesicles with antibacterial capacity from neutrophilic granulocytes.
Journal of Extracellular Vesicles ( IF 15.5 ) Pub Date : 2019-12-09 , DOI: 10.1080/20013078.2019.1698889
Ákos M Lőrincz 1 , Balázs Bartos 1 , Dávid Szombath 1 , Viktória Szeifert 1 , Csaba I Timár 1 , Lilla Turiák 2 , László Drahos 2 , Ágnes Kittel 3 , Dániel S Veres 4 , Ferenc Kolonics 1 , Attila Mócsai 1 , Erzsébet Ligeti 1
Affiliation  

Production of extracellular vesicles (EVs) involved in intercellular communication is a common capacity of most cell types. Upon encountering opsonized microorganisms, neutrophilic granulocytes release EVs that compromise bacterial growth. We carried out a systematic investigation of the involvement of potential opsonin receptors in EV-generation from human and murine neutrophils. Applying flow cytometric, proteomic and functional analysis as well as using genetically modified mice, we demonstrate that formation of antibacterial EVs depends upon stimulation of the multifunctional Mac-1 integrin complex, also called as complement receptor 3 (CR3), whereas activation of immunoglobulin binding Fc receptors or pattern recognition receptors alone or in combination is ineffective. Mac-1/CR3 stimulation and downstream tyrosine kinase signalling affect both the numbers, the cargo content and the antibacterial capacity of the produced vesicles. In contrast, Mac-1/CR3 signalling is not required for spontaneous EV formation, clearly indicating the existence of separate molecular pathways in EV biogenesis. We propose that EVs are "tailor-made" with different composition and functional properties depending on the environmental circumstances.

中文翻译:

Mac-1整合素在嗜中性粒细胞产生具有抗菌能力的细胞外囊泡中的作用。

参与细胞间通讯的细胞外囊泡(EVs)的生产是大多数细胞类型的普遍能力。遇到调理过的微生物后,嗜中性粒细胞释放出损害细菌生长的电动汽车。我们对潜在的调理素受体参与人和鼠中性粒细胞的EV产生进行了系统的研究。应用流式细胞仪,蛋白质组学和功能分析以及使用转基因小鼠,我们证明了抗菌电动车的形成取决于多功能Mac-1整联蛋白复合物(也称为补体受体3(CR3))的刺激,而免疫球蛋白结合的激活单独或组合使用的Fc受体或模式识别受体无效。Mac-1 / CR3刺激和下游酪氨酸激酶信号传导会影响所产生的囊泡的数量,货物含量和抗菌能力。相反,自发的EV形成不需要Mac-1 / CR3信号,这清楚地表明了EV生物发生中存在单独的分子途径。我们建议电动汽车是“量身定制的”,具有不同的成分和功能特性,具体取决于环境条件。
更新日期:2020-04-20
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