The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation

被引：89

作者：

Murthy, Pranav ^{[1
]}

Durco, Filip ^{[2
]}

Miller-Ocuin, Jennifer L. ^{[1
]}

Takedai, Teiko ^{[1
]}

Shankar, Shruthi ^{[1
]}

Liang, Xiaoyan ^{[1
]}

Liu, Xiao ^{[3
]}

Cui, Xiangdong ^{[1
]}

Sachdev, Ulka ^{[1
]}

Rath, Dominik ^{[2
]}

Lotze, Michael T. ^{[1
]}

Zeh, Herbert J., III ^{[1
]}

Gawaz, Meinrad ^{[2
]}

Weber, Alexander N. ^{[3
]}

Vogel, Sebastian ^{[2
,4
]}

机构：

[1] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA

[2] Eberhard Karls Univ Tubingen, Dept Cardiol & Cardiovasc Dis, Tubingen, Germany

[3] Eberhard Karls Univ Tubingen, Dept Immunol, Interfac Inst Cell Biol, Tubingen, Germany

[4] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15260 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 483卷 / 01期

关键词：

Platelets; NLRP3; Bruton's tyrosine kinase; Aggregation; Thrombosis; MICE; CASPASE-1; REGULATOR; MONOCYTES; APOPTOSIS; MUTATION; COLLAGEN; RECEPTOR; PROTEIN; IMMUNE;

D O I：

10.1016/j.bbrc.2016.12.161

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cleavage of interleukin-1 beta (IL-1 beta) is a key inflammatory event in immune cells and platelets, which is mediated by nucleotide-binding domain leucine rich repeat containing protein (NLRP3)-dependent activation of caspase-1. In immune cells, NLRP3 and caspase-1 form inflammasome complexes with the adaptor proteins apoptosis-associated speck-like protein containing a CARD (ASC) and bruton's tyrosine kinase (BTK). In platelets, however, the regulatory triggers and the functional effects of the NLRP3 inflammasome are unknown. Here, we show in vitro that the platelet NLRP3 inflammasome contributes to platelet activation, aggregation, and thrombus formation. NLRP3 activity, as monitored by caspase-1 activation and cleavage and secretion of IL-1 beta, was upregulated in activated platelets, which was dependent on platelet BTK. Pharmacological inhibition or genetic ablation of BTK in platelets led to decreased platelet activation, aggregation, and in vitro thrombus formation. We identify a functionally relevant link between BTK and NLRP3 in platelets, with potential implications in disease states associated with abnormal coagulation and inflammation. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：230 / 236

页数：7

共 28 条

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