Human cytomegalovirus infection up-regulates interleukin-8 gene expression and stimulates neutrophil transendothelial migration
Human cytomegalovirus infection up-regulates interleukin-8 gene expression and stimulates neutrophil transendothelial migration
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DOI：
10.1046/j.1365-2567.1997.00310.x
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发表时间：
1997-09-01
期刊：
影响因子：
6.4
通讯作者：
Grundy, JE
中科院分区：
文献类型：
--
作者：
Craigen, JL;Yong, KL;Grundy, JE
病毒诱导的趋化因子细胞表达的改变可能在指导特定白细胞亚群迁移到感染部位方面很重要，从而在病毒发病机制中发挥关键作用。我们发现巨细胞病毒（CMV）感染人成纤维细胞后，C-X-C或α-趋化因子白细胞介素-8（IL-8）在mRNA和蛋白水平的表达显著增加。在用高传代实验室CMV毒株AD 169、Towne或Davis以及低传代临床CMV分离株Toledo或CIF感染后观察到IL-8产生增加。IL-8产生的增加具有功能性后果，如CMV感染的成纤维细胞的上清液显著增强中性粒细胞跨内皮迁移的能力所证明的。后者是独立的内皮细胞上的粘附分子表达的改变，并废除了IL-8的特异性中和抗体。内皮细胞嗜性CMV株ClFE直接感染内皮细胞，也导致增强中性粒细胞跨内皮迁移。嗜中性粒细胞在CMV在全身的传播中起重要作用，因此CMV诱导的嗜中性粒细胞募集预期会增强CMV传播。响应CMV感染的趋化因子的产生增加也可能破坏有益和破坏性免疫应答之间的精细平衡，从而可能导致病理学。
Virus-induced alterations in the cellular expression of chemokines may be important in directing the migration of specific leucocyte subsets to sites of infection, thereby playing a pivotal role in viral pathogenesis. We show here that cytomegalovirus (CMV) infection of human fibroblasts resulted in significantly increased expression of the C-X-C or alpha-chemokine interleukin-8 (IL-8), at both the mRNA and protein levels. Increased IL-8 production was seen following infection with the high passage laboratory CMV strains AD169, Towne, or Davis, as well as the low passage clinical CMV isolates Toledo or CIF. The increase in IL-8 production had functional consequences, as demonstrated by the ability of supernatants from CMV-infected fibroblasts to significantly enhance neutrophil transendothelial migration. The latter was independent of alterations in adhesion molecule expression on the endothelial cells, and was abrogated by neutralizing antibodies specific for IL-8. Direct infection of endothelium with the endothelial cell-tropic CMV strain ClFE, also resulted in enhanced neutrophil transendothelial migration. Neutrophils play an important role in the dissemination of CMV throughout the body, and thus CMV-induced neutrophil recruitment would be expected to enhance CMV dissemination. Increased production of chemokines in response to CMV infection could also disrupt the fine balance between a beneficial and a destructive immune response, thereby potentially contributing to pathology.