Modification of endothelial cell functions by hantaan virus infection: prolonged hyper-permeability induced by TNF-alpha of hantaan virus-infected endothelial cell monolayers
Modification of endothelial cell functions by hantaan virus infection: prolonged hyper-permeability induced by TNF-alpha of hantaan virus-infected endothelial cell monolayers
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DOI：
10.1007/s00705-004-0306-y
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发表时间：
2004-07-01
影响因子：
2.7
通讯作者：
Morikawa, S
中科院分区：
文献类型：
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作者：
Niikura, M;Maeda, A;Morikawa, S
严重的血管渗漏是汉坦病毒感染发病机制的核心。然而，无论在体内还是体外，都没有证据表明汉坦病毒感染内皮细胞会直接导致明显的细胞损伤或形态学改变。在这项研究中，我们研究了汉滩病毒（HTNV）感染是否改变内皮细胞单层的屏障功能后，暴露于促炎细胞因子。低水平（1 ng/ml）的肿瘤坏死因子-α最初增加了HTNV感染和未感染单层的渗透性。然而，此后，这些单层显示出显著差异。HTNV感染的单层细胞在长达4天的实验期间保持不可逆的高渗透性，而未感染的单层细胞完全恢复了屏障功能。HTNV感染的单层细胞的长期高渗透性与单层细胞的细胞死亡或间隙形成无关，并且独立于其一氧化氮或前列腺素的产生。这些结果是汉坦病毒感染改变内皮细胞单层屏障功能的第一个证据，并表明HTNV感染的内皮细胞可能有助于通过延长对细胞因子的反应增加血管渗漏。
Serious vascular leakage is central to the pathogenesis of hantavirus infections. However, there is no evidence suggesting the hantavirus infection of endothelial cells directly causes obvious cell damage or morphological alteration either in vivo or in vitro. In this study, we examined whether Hantaan virus (HTNV) infection modifies the barrier function of endothelial cell monolayers upon the exposure to pro-inflammatory cytokines. Low levels (1 ng/ml) of tumor necrosis factor-alpha initially increased the permeability in both HTNV-infected and uninfected monolayers similarly. Thereafter, however, these monolayers showed significant difference. The HTNV-infected monolayers remained irreversibly hyper-permeable during the experimental period up to 4 days, while the uninfected monolayers completely recovered the barrier function. The prolonged hyper-permeability of HTNV-infected monolayers was not associated with cell death or gap formation in the monolayers, and was independent from their nitric oxide or prostaglandin production. These results are the first evidence that hantavirus infection modifies barrier function of endothelial cell monolayers and suggest that HTNV-infection of endothelial cells may contribute to the increased vascular leakage through the prolonged response to cytokines.