van den Boogaard Florry E, Schouten Marcel, de Stoppelaar Sacha F, Roelofs Joris J T H, Brands Xanthe, Schultz Marcus J, van't Veer Cornelis, van der Poll Tom
1Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Amsterdam, The Netherlands. 2Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands. 3Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. 4Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. 5Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, The Netherlands. 6Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Crit Care Med. 2015 Mar;43(3):e75-83. doi: 10.1097/CCM.0000000000000853.
Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, that is, by facilitating clot formation, production of antimicrobial proteins, and interaction with neutrophils. We studied the effect of thrombocytopenia during murine pneumococcal pneumonia.
Animal study.
University research laboratory.
Mice.
Pneumonia was induced by intranasal inoculation of S. pneumoniae. Platelets were depleted by anti-mouse thrombocyte serum; controls received nonimmunogenic serum. In separate studies, mice were treated with the platelet P2Y12 receptor inhibitor clopidogrel or placebo.
Thrombocytopenic mice (platelet counts < 1% of uninfected controls) showed a reduced survival during pneumococcal pneumonia (27% vs 75% among controls; p = 0.003), which was associated with higher bacterial loads in lungs, spleen, and blood. Thrombocytopenic mice showed enhanced coagulation activation (thrombin-antithrombin complexes) in plasma. Proinflammatory cytokine levels were higher in plasma but not in lungs of thrombocytopenic mice. Although clopidogrel treatment strongly prolonged the bleeding time, it did not impact on bacterial loads during pneumococcal pneumonia.
Platelets play a protective role during pneumococcal pneumonia independent of their aggregation.
肺炎链球菌是社区获得性肺炎最常见的致病病原体。在患者中，血小板减少与肺炎的不良预后相关。血小板可通过多种方式调节宿主对感染的反应，即促进血栓形成、抗菌蛋白的产生以及与中性粒细胞的相互作用。我们研究了小鼠肺炎球菌肺炎期间血小板减少的影响。
动物研究。
大学研究实验室。
小鼠。
通过鼻内接种肺炎链球菌诱导肺炎。用抗小鼠血小板血清使血小板减少；对照组接受非免疫原性血清。在单独的研究中，小鼠用血小板P2Y12受体抑制剂氯吡格雷或安慰剂治疗。
血小板减少的小鼠（血小板计数<未感染对照组的1%）在肺炎球菌肺炎期间存活率降低（对照组为75%，血小板减少组为27%；p = 0.003），这与肺、脾和血液中更高的细菌载量相关。血小板减少的小鼠血浆中凝血激活增强（凝血酶 - 抗凝血酶复合物）。血小板减少小鼠的血浆中促炎细胞因子水平较高，但肺中没有。尽管氯吡格雷治疗显著延长了出血时间，但它对肺炎球菌肺炎期间的细菌载量没有影响。
血小板在肺炎球菌肺炎期间发挥保护作用，与其聚集无关。
