Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation.
Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation.
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DOI：
10.1038/s41467-018-03925-2
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发表时间：
2018-04-18
影响因子：
16.6
通讯作者：
Schulz C
中科院分区：
文献类型：
--
作者：
Pircher J;Czermak T;Ehrlich A;Eberle C;Gaitzsch E;Margraf A;Grommes J;Saha P;Titova A;Ishikawa-Ankerhold H;Stark K;Petzold T;Stocker T;Weckbach LT;Novotny J;Sperandio M;Nieswandt B;Smith A;Mannell H;Walzog B;Horst D;Soehnlein O;Massberg S;Schulz C
白细胞释放的抗微生物肽有助于病原体的消除和免疫系统的激活。它们在血栓形成中的作用尚不完全清楚。在这里，我们表明，凯萨林菌素LL-37是丰富的血栓从急性心肌梗死患者。其小鼠同源物CRAMP存在于血管损伤后的小鼠动脉血栓中，并且主要来源于循环中性粒细胞。骨髓嵌合体小鼠中造血CRAMP的缺乏减少血小板募集和血栓形成。LL-37和CRAMP均通过蛋白酪氨酸激酶Src/Syk和磷脂酶C使糖蛋白VI受体参与下游信号传导而在体外诱导血小板活化。除了急性血栓形成之外，LL-37/CRAMP依赖性血小板活化通过调节中性粒细胞向组织中的募集和外渗来促进其他炎性病症中的血小板-中性粒细胞相互作用。CRAMP的缺乏消除了酸诱导的肺损伤，这是一种依赖于血小板-中性粒细胞相互作用的小鼠肺炎模型。我们认为LL-37/CRAMP代表血小板活化和血栓炎症的重要介质。Cathelicidin是一种抗菌肽，可以消除病原体并促进先天免疫反应。在这里，作者表明嗜中性粒细胞衍生的LL-37/CRAMP诱导血小板活化并促进动脉血栓形成和血栓炎症。
Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet–neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet–neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation. Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.
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影响因子：
4.4
作者：
Cadroy, Y;Dupouy, D;Plaisancié, H
通讯作者：
Plaisancié, H
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
82.9
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
通讯作者：
Brauner, Annelie
影响因子：
3.7
作者：
Barlow PG;Svoboda P;Mackellar A;Nash AA;York IA;Pohl J;Davidson DJ;Donis RO
通讯作者：
Donis RO
DOI：
10.1161/01.atv.0000223901.08459.57
发表时间：
2006-07-01
影响因子：
8.7
作者：
Edfeldt, Kristina;Agerberth, Birgitta;Yan, Zhong-qun
通讯作者：
Yan, Zhong-qun