Platelets attenuate production of cytokines and nitric oxide by macrophages in response to bacterial endotoxin
Platelets attenuate production of cytokines and nitric oxide by macrophages in response to bacterial endotoxin
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DOI：
10.3109/09537104.2015.1103369
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发表时间：
2016-01-01
期刊：
影响因子：
3.3
通讯作者：
Tsuji, Tsutomu
中科院分区：
文献类型：
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作者：
Ando, Yusuke;Oku, Teruaki;Tsuji, Tsutomu
关于血小板在免疫应答中的作用，已经积累了相当多的证据。在本研究中，我们研究了血小板对巨噬细胞的功能调节。当小鼠骨髓源性巨噬细胞（BMDM）与血小板共培养时，BMDM响应于细菌内毒素（LPS）和酵母聚糖产生较低水平的一氧化氮（NO）、肿瘤坏死因子-α（TNF）-α和白细胞介素（IL）-6。巨噬细胞对LPS敏感性的减弱似乎是由血小板分泌的可溶性因子介导的。如通过RT-qPCR分析的，在用血小板条件培养基培养的LPS刺激的BMDM中，NOS 2（iNOS）、TNF-α和IL-6的mRNA水平也降低。血小板条件培养基抑制巨噬细胞NO产生的能力在Superose 6柱上的凝胶过滤层析后以高分子量级分（>670 kDa）回收。这些结果表明，血小板控制巨噬细胞的易感性，以防止过度反应的LPS和提供机制洞察到以前的报告，实验性血小板减少症加重器官衰竭的LPS诱导的内毒素血症。
Considerable evidence has been accumulated concerning the roles of platelets in immune responses. In the present study, we examined the functional modulation of macrophages by platelets. When mouse bone marrow-derived macrophages (BMDMs) were co-cultured with platelets, BMDMs produced lower levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF)-alpha, and interleukin (IL)-6 in response to a bacterial endotoxin (LPS) and zymosan. The attenuation in the macrophage susceptibility to LPS appeared to be mediated by soluble factors secreted from platelets. The mRNA levels of NOS2 (iNOS), TNF-alpha, and IL-6 in LPS-stimulated BMDMs that had been cultured with a conditioned medium of platelets were also decreased as analyzed by RT-qPCR. The ability of the platelet-conditioned medium to suppress macrophage NO production was recovered in a high-molecular-weight fraction (>670 kDa) after gel-filtration chromatography on a Superose 6 column. These results suggest that platelets control the susceptibility of macrophages to prevent excessive responses to LPS and provide mechanistic insight into a previous report that experimental thrombocytopenia aggravated organ failure in LPS-induced endotoxemia.