Platelet Depletion Impairs Host Defense to Pulmonary Infection with Pseudomonas aeruginosa in Mice
Platelet Depletion Impairs Host Defense to Pulmonary Infection with Pseudomonas aeruginosa in Mice
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DOI：
10.1165/rcmb.2017-0083oc
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发表时间：
2018-03-01
影响因子：
6.4
通讯作者：
Page, Clive P.
中科院分区：
文献类型：
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作者：
Amison, Richard T.;O'Shaughnessy, Blaze G.;Page, Clive P.
血小板在暴露于过敏和非过敏刺激后与肺炎性细胞募集有关，但对血小板在铜绿假单胞菌肺部感染反应中的作用知之甚少。在这项研究中，我们在铜绿假单胞菌肺部感染的小鼠模型中，研究了实验性血小板耗尽对一系列炎症和细菌参数的影响，以及它们随后对死亡率的影响。感染铜绿假单胞菌的小鼠，除肺内血小板聚集外，还可引起轻微但严重的外周血小板减少。在感染的小鼠中，通过BAL液和血浆中血小板衍生介质-4和β-血栓球蛋白水平的增加，检测到血小板活化增加。在循环血小板耗尽的小鼠中，感染24小时后肺内中性粒细胞募集显著减少，而与未耗尽血小板的对照小鼠相比，全身传播细菌的发生率显著增加。此外，缺乏循环中的血小板的细菌感染小鼠的死亡率也增加了。这项工作证明了血小板在宿主对革兰氏阴性细菌呼吸道感染的反应中所起的作用。
Platelets have been implicated in pulmonary inflammatory cell recruitment after exposure to allergic and nonallergic stimuli, but little is known about the role of platelets in response to pulmonary infection with Pseudomonas aeruginosa. In this study, we have investigated the impact of the experimental depletion of circulating platelets on a range of inflammatory and bacterial parameters, and their subsequent impact on mortality in a murine model of pulmonary infection with P. aeruginosa. P. aeruginosa infection in mice induced a mild, but significant, state of peripheral thrombocytopenia in addition to pulmonary platelet accumulation. Increased platelet activation was detected in infected mice through increased levels of the platelet-derived mediators, platelet factor-4 and beta-thromboglobulin, in BAL fluid and blood plasma. In mice depleted of circulating platelets, pulmonary neutrophil recruitment was significantly reduced 24 hours after infection, whereas the incidence of systemic dissemination of bacteria was significantly increased compared with non-platelet-depleted control mice. Furthermore, mortality rates were increased in bacterial-infected mice depleted of circulating platelets. This work demonstrates a role for platelets in the host response toward a gram-negative bacterial respiratory infection.