Tumpey T M, Cheng H, Cook D N, Smithies O, Oakes J E, Lausch R N
Department of Microbiology and Immunology, University of South Alabama, Mobile 36688, USA.
J Virol. 1998 May;72(5):3705-10. doi: 10.1128/JVI.72.5.3705-3710.1998.
Prior studies in our laboratory have suggested that the CC chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) may be an important mediator in the blinding ocular inflammation which develops following herpes simplex virus type 1 (HSV-1) infection of the murine cornea. To directly test this hypothesis, MIP-1alpha-deficient (-/-) mice and their wild-type (+/+) counterparts were infected topically on the scarified cornea with 2.5 x 10(5) PFU of HSV-1 strain RE and subsequently graded for corneal opacity. Four weeks postinfection (p.i.), the mean corneal opacity score of -/- mice was 1.1 +/- 0.3 while that of the +/+ mice was 3.7 +/- 0.5. No detectable infiltrating CD4+ T cells were seen histologically at 14 or 21 days p.i. in -/- animals, whereas the mean CD4+ T-cell count per field (36 fields counted) in +/+ hosts was 26 +/- 2 (P < 0.001). In addition, neutrophil counts in the -/- mouse corneas were reduced by >80% in comparison to the wild-type controls. At 2 weeks p.i., no interleukin-2 or gamma interferon could be detected in six of seven -/- mice, whereas both T-cell cytokines were readily demonstrable in +/+ mouse corneas. Also, MIP-2 and monocyte chemoattractant protein-1 protein levels were significantly lower in MIP-1alpha -/- mouse corneas than in +/+ host corneas, suggesting that MIP-1alpha directly, or more likely indirectly, influences the expression of other chemokines. Interestingly, despite the paucity of infiltrating cells, HSV-1 clearance from the eyes of -/- mice was not significantly different from that observed in +/+ hosts. We conclude that MIP-1alpha is not needed to control virus growth in the cornea but is essential for the development of severe stromal keratitis.
我们实验室之前的研究表明，CC趋化因子巨噬细胞炎性蛋白-1α（MIP-1α）可能是单纯疱疹病毒1型（HSV-1）感染小鼠角膜后发生的致盲性眼部炎症中的一种重要介质。为了直接验证这一假设，将MIP-1α基因缺陷（-/-）小鼠及其野生型（+/+）对照在划痕角膜上局部感染2.5×10⁵噬斑形成单位（PFU）的HSV-1 RE株，随后对角膜混浊程度进行分级。感染后4周（p.i.），-/-小鼠的平均角膜混浊评分为1.1±0.3，而+/+小鼠为3.7±0.5。在感染后14天或21天，组织学检查在-/-动物中未见到可检测到的浸润性CD4⁺ T细胞，而在+/+宿主中每视野（共计数36个视野）的平均CD4⁺ T细胞计数为26±2（P<0.001）。此外，与野生型对照相比，-/-小鼠角膜中的中性粒细胞计数减少了80%以上。在感染后2周，7只-/-小鼠中有6只检测不到白细胞介素-2或γ干扰素，而在+/+小鼠角膜中这两种T细胞细胞因子都很容易检测到。而且 MIP-1α -/-小鼠角膜中的MIP-2和单核细胞趋化蛋白-1蛋白水平显著低于+/+宿主角膜，这表明MIP-1α直接或更可能间接影响其他趋化因子的表达。有趣的是，尽管浸润细胞很少，但-/-小鼠眼中HSV-1的清除与+/+宿主中观察到的情况没有显著差异。我们得出结论，控制角膜中的病毒生长不需要MIP-1α，但它对于严重基质性角膜炎的发展至关重要。
