1 Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science and.
2 British Heart Foundation Centre for Cardiovascular Research, King's College London, London, United Kingdom; and.
Am J Respir Cell Mol Biol. 2018 Mar;58(3):331-340. doi: 10.1165/rcmb.2017-0083OC.
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 β-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.
血小板被认为参与了暴露于变应原和非变应原刺激后的肺部炎症细胞募集,但对于血小板在铜绿假单胞菌肺部感染中的作用知之甚少。在这项研究中,我们研究了循环血小板耗竭对一系列炎症和细菌参数的影响,以及它们对铜绿假单胞菌肺部感染小鼠模型死亡率的后续影响。铜绿假单胞菌感染小鼠除了肺部血小板聚集外,还引起外周血小板轻度但显著减少。通过检测感染小鼠的血小板衍生介质血小板因子 4 和β-血栓球蛋白在 BAL 液和血浆中的水平,发现血小板激活增加。与非血小板耗竭对照组小鼠相比,循环血小板耗竭的小鼠在感染后 24 小时肺部中性粒细胞募集显著减少,而细菌全身播散的发生率显著增加。此外,血小板耗竭的细菌感染小鼠死亡率增加。这项工作表明血小板在宿主对革兰氏阴性细菌性呼吸道感染的反应中起作用。