Neutrophil infiltration to the brain is platelet-dependent, and is reversed by blockade of platelet GPIbα.
Neutrophil infiltration to the brain is platelet-dependent, and is reversed by blockade of platelet GPIbα.
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DOI：
10.1111/imm.12892
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发表时间：
2018-06
期刊：
影响因子：
6.4
通讯作者：
Allan SM
中科院分区：
文献类型：
--
作者：
Giles JA;Greenhalgh AD;Denes A;Nieswandt B;Coutts G;McColl BW;Allan SM
中性粒细胞是先天免疫反应的关键组成部分，提供宿主防御感染并被招募到非微生物损伤部位。血小板作为中性粒细胞向炎症部位外渗的触发因素，但这些相互作用的机制和组织特异性方面目前尚不清楚。在这里，我们使用细菌内毒素在小鼠体内触发不同组织的先天炎症反应，并测量有或没有血小板减少的中性粒细胞侵袭。我们发现血小板是中性粒细胞向大脑、腹膜和皮肤浸润所必需的。腹膜和皮肤的中性粒细胞数量不会高于基础水平，当血小板数量减少时，大脑中的中性粒细胞数量会减少（约60%）。相比之下，肺部中性粒细胞浸润不受血小板减少的影响，在肺部炎症期间血小板减少的小鼠中，CXCL - 1（2.4倍）和CCL5（1.4倍）的上调作为一种代偿机制。在以血小板受体为靶点的脑炎症中，GPIbα导致血小板介导的中性粒细胞侵袭显著减少（44%），同时维持循环中的血小板数量。这些结果表明，治疗性阻断血小板GPIbα可以限制过度炎症的有害影响，同时最大限度地减少大脑血小板减少的出血并发症。数据还表明，该药物能够靶向脑卒中和相关疾病中的破坏性脑炎症，而不会损害肺免疫，从而降低患肺炎的风险，肺炎是脑卒中后的主要并发症。总之，我们的数据揭示了血小板在中性粒细胞浸润到包括脑在内的各种组织中的重要作用，因此暗示血小板是脑血管炎症疾病或损伤的关键、可靶向成分。
Neutrophils are key components of the innate immune response, providing host defence against infection and being recruited to non‐microbial injury sites. Platelets act as a trigger for neutrophil extravasation to inflammatory sites but mechanisms and tissue‐specific aspects of these interactions are currently unclear. Here, we use bacterial endotoxin in mice to trigger an innate inflammatory response in different tissues and measure neutrophil invasion with or without platelet reduction. We show that platelets are essential for neutrophil infiltration to the brain, peritoneum and skin. Neutrophil numbers do not rise above basal levels in the peritoneum and skin and are decreased (~60%) in the brain when platelet numbers are reduced. In contrast neutrophil infiltration in the lung is unaffected by platelet reduction, up‐regulation of CXCL‐1 (2·4‐fold) and CCL5 (1·4‐fold) acting as a compensatory mechanism in platelet‐reduced mice during lung inflammation. In brain inflammation targeting platelet receptor GPIbα results in a significant decrease (44%) in platelet‐mediated neutrophil invasion, while maintaining platelet numbers in the circulation. These results suggest that therapeutic blockade of platelet GPIbα could limit the harmful effects of excessive inflammation while minimizing haemorrhagic complications of platelet reduction in the brain. The data also demonstrate the ability to target damaging brain inflammation in stroke and related disorders without compromising lung immunity and hence risk of pneumonia, a major complication post stroke. In summary, our data reveal an important role for platelets in neutrophil infiltration to various tissues, including the brain, and so implicate platelets as a key, targetable component of cerebrovascular inflammatory disease or injury.
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DOI：
10.1126/science.1256478
发表时间：
2014-12-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Sreeramkumar V;Adrover JM;Ballesteros I;Cuartero MI;Rossaint J;Bilbao I;Nácher M;Pitaval C;Radovanovic I;Fukui Y;McEver RP;Filippi MD;Lizasoain I;Ruiz-Cabello J;Zarbock A;Moro MA;Hidalgo A
通讯作者：
Hidalgo A
影响因子：
5.4
作者：
Giles, James A.;Greenhalgh, Andrew D.;Davies, Claire L.;Denes, Adam;Shaw, Tovah;Coutts, Graham;Rothwell, Nancy J.;McColl, Barry W.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
3.3
作者：
Gardiner, Elizabeth E.;Arthur, Jane F.;Berndt, Michael C.
通讯作者：
Berndt, Michael C.
影响因子：
5.3
作者：
Schwab, Jan M.;Zhang, Yi;Kopp, Marcel A.;Brommer, Benedikt;Popovich, Phillip G.
通讯作者：
Popovich, Phillip G.
影响因子：
5.3
作者：
McColl, Barry W.;Rothwell, Nancy J.;Allan, Stuart M.
通讯作者：
Allan, Stuart M.