Absence of macrophage inflammatory protein-1alpha prevents the development of blinding herpes stromal keratitis.
Absence of macrophage inflammatory protein-1alpha prevents the development of blinding herpes stromal keratitis.
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巨噬细胞炎症蛋白-1α 的缺失可防止致盲性疱疹性基质角膜炎的发展。
DOI：
10.1128/jvi.72.5.3705-3710.1998
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发表时间：
1998
影响因子：
5.4
通讯作者：
Lausch,RN
中科院分区：
文献类型：
--
作者：
Tumpey,TM;Cheng,H;Cook,DN;Smithies,O;Oakes,JE;Lausch,RN
本实验室先前的研究表明，CC趋化因子巨噬细胞炎性蛋白-1 α（MIP-1α）可能是小鼠角膜单纯疱疹病毒1型（HSV-1）感染后致盲性眼部炎症的重要介质。为了直接检验这一假设，用2.5 × 105 PFU的HSV-1菌株RE局部感染MIP-1α缺陷型（−/−）小鼠及其野生型（+/+）小鼠的划痕角膜，随后对角膜混浊进行分级。感染后4周（p.i.），- /-小鼠的平均角膜混浊评分为1.1 ± 0.3，而+/+小鼠的平均角膜混浊评分为3.7 ± 0.5。在感染后14或21天，组织学上未观察到可检测到的浸润性CD 4 +T细胞。在−/−动物中，而在+/+宿主中，每个视野（计数36个视野）的平均CD 4 + T细胞计数为26 ± 2（P< 0.001）。此外，与野生型对照组相比，−/−小鼠角膜中的中性粒细胞计数减少>80%。在注射后2周，在7只−/−小鼠中的6只中没有检测到白细胞介素-2或γ干扰素，而在+/+小鼠角膜中很容易证明这两种T细胞细胞因子。此外，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，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，尽管缺乏浸润细胞，但HSV-1从−/−小鼠眼中的清除与在+/+宿主中观察到的没有显著差异。我们的结论是，MIP-1α是不需要控制病毒在角膜中的生长，但对于严重的基质角膜炎的发展是必不可少的。
Prior studies in our laboratory have suggested that the CC chemokine macrophage inflammatory protein-1α (MIP-1α) 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-1α-deficient (−/−) mice and their wild-type (+/+) counterparts were infected topically on the scarified cornea with 2.5 × 105PFU 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-1α −/− mouse corneas than in +/+ host corneas, suggesting that MIP-1α 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-1α is not needed to control virus growth in the cornea but is essential for the development of severe stromal keratitis.