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纤连蛋白促进静脉微血管中的免疫血栓失调。

Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature.

机构信息

Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.

Walter Brendel Centre of Experimental Medicine, University Hospital, Ludwig-Maximilians-Universität München (LMU) Munich, Munich, Germany.

出版信息

Front Immunol. 2023 Feb 8;14:1078005. doi: 10.3389/fimmu.2023.1078005. eCollection 2023.

DOI:10.3389/fimmu.2023.1078005
PMID:36845099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9945350/
Abstract

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

摘要

微血管免疫血栓调节紊乱是严重全身炎症性疾病发病机制中的一个关键过程。然而，控制炎症微血管中免疫血栓形成的机制仍知之甚少。在这里，我们报告在全身炎症状态下，细胞外基质糖蛋白 vitronectin（VN）在血管内形成支架，支持聚集的血小板与免疫细胞和静脉内皮的相互作用。阻断 VN 受体糖蛋白（GP）IIb/IIIa 干扰了这种细胞间相互作用，并有效地防止了微血管血栓形成。与这些实验数据一致的是，在患有非感染性（胰腺炎相关）或感染性（2019 年冠状病毒病（COVID-19）相关）严重全身炎症反应的患者的肺部微血管中，VN 被发现特别丰富。因此，靶向 VN-GPIIb/IIIa 轴似乎是一种很有前途的、已经可行的策略，可以对抗全身炎症性疾病中的微血管免疫血栓调节紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/db7e0fbfaeb0/fimmu-14-1078005-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/91b9217fbe91/fimmu-14-1078005-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/0be13ae33339/fimmu-14-1078005-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/b8763d191b85/fimmu-14-1078005-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/db7e0fbfaeb0/fimmu-14-1078005-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/91b9217fbe91/fimmu-14-1078005-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/0be13ae33339/fimmu-14-1078005-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/b8763d191b85/fimmu-14-1078005-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b478/9945350/db7e0fbfaeb0/fimmu-14-1078005-g004.jpg

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本文引用的文献

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Clinical spectrum of ischaemic arterial diseases associated with COVID-19: a series of four illustrative cases.与新型冠状病毒肺炎相关的缺血性动脉疾病临床谱：4例说明性病例系列
Eur Heart J Case Rep. 2020 Dec 25;5(1):ytaa488. doi: 10.1093/ehjcr/ytaa488. eCollection 2021 Jan.
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The ADAMTS13-von Willebrand factor axis in COVID-19 patients.新冠病毒感染患者中的ADAMTS13-血管性血友病因子轴
J Thromb Haemost. 2021 Feb;19(2):513-521. doi: 10.1111/jth.15191. Epub 2020 Dec 18.
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Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin.
附录：与一种可能源自蝙蝠的新型冠状病毒相关的肺炎疫情。
Nature. 2020 Dec;588(7836):E6. doi: 10.1038/s41586-020-2951-z.
4
Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated With Respiratory Failure and Coagulopathy.新型冠状病毒肺炎肺炎中的免疫血栓调节紊乱与呼吸衰竭和凝血病有关。
Circulation. 2020 Sep 22;142(12):1176-1189. doi: 10.1161/CIRCULATIONAHA.120.048488. Epub 2020 Jul 28.
5
Vitronectin stabilizes intravascular adhesion of neutrophils by coordinating β2 integrin clustering.纤连蛋白通过协调β2 整合素聚集稳定中性粒细胞的血管内黏附。
Haematologica. 2021 Oct 1;106(10):2641-2653. doi: 10.3324/haematol.2019.226241.
6
Endothelial cells orchestrate COVID-19 coagulopathy.内皮细胞在新型冠状病毒肺炎凝血病中起关键作用。
Lancet Haematol. 2020 Aug;7(8):e553-e555. doi: 10.1016/S2352-3026(20)30215-5. Epub 2020 Jun 30.
7
Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study.新型冠状病毒肺炎相关凝血病中的内皮病变：来自一项单中心横断面研究的证据
Lancet Haematol. 2020 Aug;7(8):e575-e582. doi: 10.1016/S2352-3026(20)30216-7. Epub 2020 Jun 30.
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