Platelets support pulmonary recruitment of neutrophils in abdominal sepsis
Platelets support pulmonary recruitment of neutrophils in abdominal sepsis
复制标题
DOI：
10.1097/ccm.0b013e31819ceb71
复制
发表时间：
2009-04-01
影响因子：
8.8
通讯作者：
Thorlacius, Henrik
中科院分区：
文献类型：
--
作者：
Asaduzzaman, Muhammad;Lavasani, Shahram;Thorlacius, Henrik
目标。最近的研究结果表明，血小板不仅调节血栓形成和止血，而且可能参与促炎活动。在此，我们假设血小板可能通过激活和启动循环中性粒细胞进入肺部而在脓毒症中发挥作用。设计：前瞻性实验研究。大学医院研究中心。雄性C57BL/6小鼠。测定盲肠结扎穿刺（CLP）后肺水肿、支气管肺泡中性粒细胞浸润、髓过氧化物酶水平、膜活化复合物-1 （Mac-1）对中性粒细胞和CXC趋化因子、巨噬细胞炎性蛋白-2、细胞因子诱导的中性粒细胞趋化因子的表达和功能。小鼠在CLP诱导前接受血小板消耗抗体以及针对p -选择素糖蛋白配体-1和Mac-1的抗体。测量和主要结果。CLP引起显著的肺损伤，表现为中性粒细胞浸润、CXC趋化因子水平升高和肺水肿形成。此外，CLP上调中性粒细胞中Mac-1的表达，增加循环中与血小板结合的中性粒细胞的数量。有趣的是，血小板耗竭使clp诱导的水肿和支气管肺泡间隙中性粒细胞募集减少了60%。此外，血小板消耗降低了中性粒细胞上Mac-1的表达。另一方面，抑制p -选择素糖蛋白配体-1可消除clp诱导的中性粒细胞-血小板聚集，但对中性粒细胞Mac-1的表达无影响。结论：这些数据表明，在腹部脓毒症中，血小板通过上调Mac-1在调节肺中性粒细胞浸润和水肿形成中起关键作用。（重症护理医学2009；37:1389-1396）
Objective. Recent findings Indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment Into the lung.Design: Prospective experimental study.Setting. University Hospital Research Unit.Subject. Male C57BL/6 mice.Interventions. Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction.Measurements and Main Results. CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1.Conclusions: These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis. (Crit Care Med 2009; 37:1389-1396)