Role of MIP-2 in neutrophil migration and tissue injury in the herpes simplex virus-1-infected cornea.
Role of MIP-2 in neutrophil migration and tissue injury in the herpes simplex virus-1-infected cornea.
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发表时间：
1998-09
影响因子：
4.4
通讯作者：
Xiao‐Tian Yan;Terrence M. Tumpey;Steve L. Kunkel;J. Oakes;R. Lausch
中科院分区：
文献类型：
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作者：
Xiao‐Tian Yan;Terrence M. Tumpey;Steve L. Kunkel;J. Oakes;R. Lausch
目的中性粒细胞是最主要的细胞类型，最初迁移到单纯疱疹病毒1型(HSV-1)感染的小鼠角膜中。研究C-X-C趋化因子、巨噬细胞炎症蛋白(MIP)-2和KC在促进这一反应中的作用。方法采用酶联免疫吸附试验检测MIP-2和KC的含量。通过结膜下接种合适的抗体，实现内源性MIP-2和KC的中和。用免疫组织化学方法检测感染的角膜中白细胞的渗入情况，并用邻二苯甲胺染料检测髓过氧化物酶活性。中性粒细胞和自然杀伤细胞的耗尽是通过腹腔注射RB6-8C5和asialo GM1抗体来完成的。结果单纯疱疹病毒1型经角膜内感染后，可刺激MIP-2和KC的产生，高峰出现在感染后48h。剂量-反应研究表明，髓过氧化物酶活性和免疫组织化学染色显示，外源性MIP-2吸引中性粒细胞的能力是KC的三到四倍。结膜下注射MIP-2中和抗体可显著减少中性粒细胞的渗入，并显著降低角膜混浊评分。相反，体内使用KC中和抗体治疗并不能抑制眼部炎症。更多的研究表明，MIP-2和KC可由角膜上皮细胞产生，IL-1可促进其产生。在体内，去除中性粒细胞可显著降低MIP-2水平，但不影响KC水平。结论MIP-2是吸引中性粒细胞进入HSV-1感染的角膜的主要趋化因子，这些细胞直接或间接地引起组织损伤。驻留的角膜细胞和炎症细胞参与了MIP-2的合成，而KC的产生似乎主要局限于角膜细胞。
PURPOSE Neutrophils are the most prominent cell type to migrate initially into the herpes simplex virus type 1 (HSV-1)-infected murine cornea. The role the C-X-C chemokines macrophage inflammatory protein (MIP)-2 and KC play in promoting this response was investigated. METHODS MIP-2 and KC were quantitated by enzyme-linked immunosorbent assay. Neutralization of endogenous MIP-2 and KC was achieved by subconjunctival inoculation of the appropriate antibody. Infected corneas were examined immunohistochemically for infiltrating leukocytes and assayed for myeloperoxidase activity using the dye o-dianisidine. Depletion of neutrophils and natural killer cells was accomplished by intraperitoneal administration of RB6-8C5 and asialo GM1 antibodies. RESULTS Herpes simplex virus type 1, when introduced intracorneally, stimulated the production of MIP-2 and KC, with peak synthesis occurring 48 hours after infection. Dose-response studies showed that exogenous MIP-2 was three to four times more potent than KC in attracting neutrophils as assessed by myeloperoxidase assay and immunohistochemical staining. Subconjunctival administration of neutralizing antibody to MIP-2 resulted in a sharp decrease in neutrophil infiltration and significantly reduced corneal opacity scores. In contrast, in vivo treatment with neutralizing antibody to KC did not suppress ocular inflammation. Additional studies indicated that MIP-2 and KC could be made by corneal epithelial cells and that production was promoted by interleukin (IL)-1. In vivo depletion of neutrophils sharply reduced MIP-2 levels but did not affect KC levels. CONCLUSIONS Collectively, the results suggest that MIP-2 is the major chemokine that attracts neutrophils into the HSV-1 infected cornea, where the cells directly or indirectly cause tissue injury. Resident corneal cells and inflammatory cells contribute to MIP-2 synthesis, whereas KC production seems to be confined largely to corneal cells.