Platelet activation by Histophilus somni and its lipooligosaccharide induces endothelial cell proinflammatory responses and platelet internalization

Platelet activation by Histophilus somni and its lipooligosaccharide induces endothelial cell proinflammatory responses and platelet internalization
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DOI:
10.1097/shk.0b013e318070c49e
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发表时间:
2008-02-01
期刊:
影响因子:
3.1
通讯作者:
Czuprynski, Charles J.
Czuprynski, Charles J.
中科院分区:
医学2区
文献类型:
--
作者:
Kuckleburg, Christopher J.;McClenahan, Dave J.;Czuprynski, Charles J.

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睡眠嗜组织菌是一种革兰氏阴性球杆菌,可引起牛的呼吸道和生殖系统疾病。系统性H. Somni感染是一种弥漫性血管炎症,可导致称为血栓性脑膜脑炎急性中枢神经系统疾病。以前,我们证明了H。Somni及其脂寡糖(LOS)激活牛血小板,导致P选择素、CD 40 L和FasL的表达。由于活化血小板已被报道诱导内皮细胞细胞因子的产生和粘附分子的表达,我们试图确定牛血小板是否诱导牛肺动脉内皮细胞的促炎和促凝变化。内皮细胞与二磷酸腺苷、H. somni或H.睡眠湖通过流式细胞术、实时聚合酶链反应和蛋白质印迹分析测量,与活化的牛血小板一起孵育显着增加粘附分子(细胞间粘附分子1,E选择素)和组织因子的表达。活化的血小板还通过实时聚合酶链反应和IL-1 β酶联免疫吸附测定来确定内皮细胞IL-1 β、单核细胞趋化蛋白1和巨噬细胞炎性蛋白Ia的脂调节表达。一个有趣的和令人惊讶的发现是,牛血小板激活H。通过透射电子显微镜观察,Somni或其LOS被牛内皮细胞内化。这种内化似乎与内皮细胞活化和指示细胞应激的形态学变化相关。这些结果表明,活化的血小板可能在H.睡眠感染
Histophilus somni is a gram-negative coccobacillus that causes respiratory and reproductive disease in cattle. The hallmark of systemic H. somni infection is diffuse vascular inflammation that can lead to an acute central nervous system disease known as thrombotic meningoencephalitis. Previously, we demonstrated that H. somni and its lipooligosaccharide (LOS) activate bovine platelets, leading to expression of P selectin, CD40L, and FasL. Because activated platelets have been reported to induce endothelial cell cytokine production and adhesion molecule expression, we sought to determine if bovine platelets induce proinflammatory and procoagulative changes in bovine pulmonary artery endothelial cells. Endothelial cells were incubated with platelets activated with adenosine diphosphate, H. somni, or H. somni LOS. Incubation with activated bovine platelets significantly increased expression of in adhesion molecules (intercellular adhesion molecule 1, E selectin) and tissue factor, as measured by flow cytometry, real-time polymerase chain reaction, and Western blot analysis. Activated platelets also Lip-regulated expression of endothelial cell IL-1 beta, monocyte chemoattractant protein 1, and macrophage inflammatory protein la as determined by real-time polymerase chain reaction and an IL-1 beta enzyme-linked immunosorbent assay. An interesting and surprising finding was that bovine platelets activated by H. somni or its LOS were internalized by bovine endothelial cells as visualized by transmission electron microscopy. This internalization seemed to correlate with endothelial cell activation and morphological changes indicative of cell stress. These findings suggest that activated platelets might play a role in promoting vascular inflammation during H. somni infection.