The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy
The implications of the upregulation of ICAM-1/VCAM-1 expression of corneal fibroblasts on the pathogenesis of allergic keratopathy
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DOI：
10.1167/iovs.04-1494
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发表时间：
2005-12-01
影响因子：
4.4
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Okada, N;Fukagawa, K;Saito, H
客观的。本研究研究了白细胞介素(IL)-4和/或肿瘤坏死因子(TNF)-α刺激下成纤维细胞上ICAM-1和VCAM-1的表达，并评估了嗜酸性粒细胞粘附对成纤维细胞活力的影响。将原代培养的人角膜成纤维细胞与IL-4、TNF-α或其组合一起孵育24小时。通过实时定量PCR和流式细胞术分析检查ICAM-1和VCAM-1的表达。将纯化的嗜酸性粒细胞与活化的成纤维细胞共培养，并使用显微镜计数粘附在成纤维细胞上的嗜酸性粒细胞的数量和受损的成纤维细胞的数量。在一项单独的试验中，对患有特应性角结膜炎和角膜溃疡的患者（八只眼睛）进行了结膜和角膜印迹细胞学检查，以评估眼表上皮的状态和炎症细胞浸润的存在。 结果。实时定量PCR和流式细胞术分析表明，IL-4和TNF-α上调VCAM-1和ICAM-1的mRNA和蛋白。 IL-5引发的嗜酸性粒细胞粘附到用IL-4和TNF-α处理的角膜成纤维细胞上，并且成纤维细胞因嗜酸性粒细胞粘附而受损。抗ICAM-1抗体和抗VCAM-1抗体抑制嗜酸性粒细胞对成纤维细胞的粘附以及成纤维细胞的损伤。印迹细胞学检查显示，在晚期鳞状上皮化生的分离眼表上皮细胞中，中性粒细胞和嗜酸性粒细胞广泛浸润。结论。当用 IL-4 和 TNF-α 激活时，角膜成纤维细胞表达 ICAM-1 和 VCAM-1。嗜酸性粒细胞可以粘附到活化的成纤维细胞上，并可以通过这些粘附分子诱导随后的成纤维细胞损伤。嗜酸性粒细胞粘附于成纤维细胞可能导致严重持续性过敏性角膜溃疡的发病机制。
OBJECTIVE. The present study investigated the expression of ICAM-1 and VCAM-1 on fibroblasts with interleukin (IL)-4 and/or tumor necrosis factor (TNF)-alpha stimulation and assessed the effect of eosinophil adhesion on fibroblast viability.METHODS. Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-alpha, or their combination for 24 hours. Expression of ICAM-1 and VCAM-1 was examined by real-time quantitative PCR and flow cytometric analysis. Purified eosinophils were cocultured with activated fibroblasts, and the number of eosinophils adhered to fibroblasts and the number of damaged fibroblasts were counted using microscopy. In a separate trial, conjunctival and corneal impression cytology was performed on patients with atopic keratoconjunctivitis and corneal ulcers (eight eyes) to assess the status of the ocular surface epithelium and the presence of inflammatory cell infiltrates.RESULTS. Real-time quantitative PCR and flow cytometric analysis revealed that both mRNA and protein of VCAM- 1 and ICAM-1 were upregulated by IL-4 and TNF-alpha. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-alpha, and the fibroblasts were damaged by eosinophil adherence. Anti-ICAM-1 antibody and anti-VCAM-1 antibody inhibited the eosinophil adherence to fibroblasts and the fibroblast damage. Impression cytology revealed extensive infiltration of neutrophil and eosinophils among isolated ocular surface epithelial cells with advanced squamous metaplasia.CONCLUSIONS. Corneal fibroblasts expressed ICAM-1 and VCAM- 1 when activated with IL-4 and TNF-alpha. Eosinophils can adhere to the activated fibroblasts and can induce subsequent fibroblast damage through these adhesion molecules. Eosinophil adhesion to fibroblasts may possibly contribute to the pathogenesis of severe persistent allergic corneal ulcers.