Systemic release of high mobility group box 1 protein during severe murine influenza
Systemic release of high mobility group box 1 protein during severe murine influenza
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DOI：
10.4049/jimmunol.181.2.1454
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发表时间：
2008-07-15
影响因子：
4.4
通讯作者：
Clark, Ian A.
中科院分区：
文献类型：
--
作者：
Alleva, Lisa M.;Budd, Alison C.;Clark, Ian A.
高细胞因子血症被认为是流感致死的机制。到目前为止，还没有工作涉及高迁移率族蛋白1（HMGB 1）在流感中的作用，与之平行的是在其他严重的促炎细胞因子综合征（例如，败血症和疟疾）的循环HMGB 1水平升高，并可能与死亡相关。使用市售的HMGB 1的ELISA，我们发现在感染流感病毒的小鼠（A/Japan/305/57）的血浆中，HMGB 1在感染后第7天（大约是死亡率的峰值时间）没有增加，并且血浆中HMGB 1的峰值水平直到感染的较晚时间（感染后第9天）才出现。与RMGB 1的晚期峰值与死亡率无关一致，向流感病毒感染的小鼠施用丙酮酸乙酯（其抑制HMGB 1的主动分泌但不抑制HMGB 1的被动释放）并不影响它们的存活。需要进一步的工作来确定流感病毒感染是否诱导HMGB 1的被动释放，以及用特异性抗体中和HMGB 1是否会改善存活率。
Hypercytokinemia is gaining recognition as the mechanism of fatality from influenza. No work to date has addressed the role of high mobility group box 1 protein (HMGB1) in influenza, the parallel being that in other severe proinflammatory cytokine syndromes (e.g., sepsis and malaria) levels of circulating HMGB1 are elevated and may correlate with death. Using a commercially available ELISA for HMGB1, we found that HMGB1 was not increased in the plasma of influenza virus-infected mice (A/Japan/305/57) on day 7 post infection, about the time of peak mortality, and peak levels of HMGB1 in the plasma did not occur until relatively late in infection, on day 9 post infection. In keeping with the late peak of RMGB1 being unassociated with mortality, administration of ethyl pyruvate, which inhibits active secretion but not passive release of HMGB1, to influenza virus-infected mice, did not affect their survival. Further work is required to determine whether influenza virus infection induces passive release of HMGB1, and whether HMGB1 neutralization with a specific Ab would improve survival.