Endothelial microparticles induce inflammation in acute lung injury.
Endothelial microparticles induce inflammation in acute lung injury.
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DOI：
10.1016/j.jss.2010.05.036
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Oldham KT
中科院分区：
文献类型：
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作者：
Buesing KL;Densmore JC;Kaul S;Pritchard KA Jr;Jarzembowski JA;Gourlay DM;Oldham KT
以前，我们已经表明，内皮微粒（EMP）注射到小鼠诱导急性肺损伤（ALI）。在这项研究中，我们假设电磁脉冲通过启动肺中细胞因子的释放，导致中性粒细胞的募集和激活来诱导ALI。C57 BL/6 J雄性小鼠（8-10周龄）静脉内注射EMP（200，000/mL）、LPS（2 mg/kg）或两者。采用酶联免疫吸附法（ELISA）检测支气管肺泡灌洗（BAL）及血清IL-1β、TNF-α水平。对H和E染色的肺切片进行形态测定分析。髓过氧化物酶（MPO）水平通过酶法和染色切片的免疫荧光法测定。EMP导致肺和全身IL-1β和TNF-α水平显著升高，这与肺中性粒细胞募集增加相关。与PBS相比，在注射EMP或LPS后肺中的MPO水平显著增加。在同时或相继用EMP和LPS处理的小鼠中，细胞因子和MPO水平比单独处理的细胞因子和MPO水平显著增加。EMP通过启动细胞因子级联反应促进肺损伤，细胞因子级联反应增加中性粒细胞的募集和随后的MPO释放。此外，用EMP和LPS治疗小鼠比单独治疗引起更大的肺损伤，这表明EMP使肺增加其他病原体的损伤。旨在减少或阻断EMP的治疗可能是减轻肺损伤的有用策略。
Previously, we have shown that endothelial microparticles (EMPs) injected into mice induce acute lung injury (ALI). In this study, we hypothesize that EMPs induce ALI by initiating cytokine release in the lung, leading to recruitment and activation of neutrophils. C57BL/6J male mice (8–10 wk old) were intravenously injected with EMPs (200,000/mL), LPS (2 mg/kg), or both. Bronchoalveolar lavage (BAL) and serum levels of IL-1β and TNF-α were analyzed by enzyme-linked immunoassay (ELISA). Morphometric analysis was performed on H and E stained lung sections. Myeloperoxidase (MPO) levels were determined via an enzymatic assay and immunofluorescence of stained sections. EMPs led to significantly increased pulmonary and systemic IL-1β and TNF-α levels, which correlated with increased neutrophil recruitment to the lung. MPO levels in the lungs were increased significantly following injection of EMPs or LPS, compared to PBS. In mice treated with EMPs and LPS either simultaneously or successively, the cytokine and MPO levels were significantly increased over that of either treatment alone. EMPs contribute to lung injury through the initiation of a cytokine cascade that increases recruitment of neutrophils and subsequent release of MPO. Furthermore, treatment of mice with both EMPs and LPS induced greater lung injury than either treatment alone, suggesting that EMPs prime the lung for increased injury by other pathogens. Therapies aimed at reducing or blocking EMPs may be a useful strategy for attenuating lung injury.