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Naoko Okada, Kazumi Fukagawa, Yoji Takano, Murat Dogru, Kazuo Tsubota, Hiroshi Fujishima, Kenji Matsumoto, Toshiharu Nakajima, Hirohisa Saito; The Implications of the Upregulation of ICAM-1/VCAM-1 Expression of Corneal Fibroblasts on the Pathogenesis of Allergic Keratopathy. Invest. Ophthalmol. Vis. Sci. 2005;46(12):4512-4518. doi: 10.1167/iovs.04-1494.
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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)-α stimulation and assessed the effect of eosinophil adhesion on fibroblast viability.
methods. Primary cultured human corneal fibroblasts were incubated with IL-4, TNF-α, 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-α. IL-5-primed eosinophils adhered to the corneal fibroblasts treated with IL-4 and TNF-α, 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-α. 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.
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