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High Expression of Chemokines Gro- (CXCL-1), IL-8 (CXCL-8), and MCP-1 (CCL-2) in Inflamed Human Corneas In Vivo

Ulrich H. M. Spandau, MD; Atiye Toksoy; Soraya Verhaart, MD; Reinhard Gillitzer, MD; Friedrich E. Kruse, MD

Arch Ophthalmol. 2003;121:825-831.

Objective  To investigate in vivo expression of chemokines in normal and inflamed human corneas, to determine whether chemokines are responsible for the recruitment of inflammatory cells.

Methods  In situ hybridization of the CXC chemokines growth-related oncogene- (Gro-) (CXCL-1), interleukin 8 (CXCL-8), macrophage interferon- inducible gene (CXCL-9), and interferon- inducible protein 10 (CXCL-10) and of the CC chemokines macrophage chemoattractant protein 1 (MCP-1) (CCL-2), macrophage inflammatory protein 1 (CCL-3), and regulated on activation, normal T-cell expressed and secreted (CCL-5) was performed to localize chemokine messenger RNA. Immunohistochemistry was used to identify the cellular infiltrate within the cornea. Three normal human eyes were compared with eyes enucleated because of chronic inflammation (n = 10), secondary to perforating injuries.

Results  In normal corneas, no chemokine expression was detected. In inflamed lesions, a high intensity of signals from Gro- (CXCL-1) and MCP-1 (CCL-2) messenger RNA was observed in limbal epithelium and from Gro- (CXCL-1), interleukin 8 (CXCL-8), and MCP-1 (CCL-2) in corneal stroma. The Gro- (CXCL-1) was the only chemokine expressed by central corneal epithelium. All other examined chemokines were only moderately expressed in limbus and corneal stroma, or barely detectable.

Conclusions  These cytokines are important agents in the cytokine network and contribute to the cell-specific and spatially restricted recruitment of neutrophils and mononuclear cells in acute inflammatory lesions of the human cornea.

Clinical Relevance  Understanding the role of chemokines in corneal inflammation may lead to the development of a selective receptor blockage of highly expressed chemokines to inhibit the recruitment of leukocyte subsets.

From the Department of Ophthalmology, Clinical Faculty of the University of Heidelberg, Mannheim, Germany (Dr Spandau); Department of Dermatology, University of Wuerzburg, Wuerzburg, Germany (Ms Toksoy and Dr Gillitzer); Department of Pathology, University of Witwatersrand, Johannesburg, South Africa (Dr Verhaart); and Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany (Dr Kruse). The authors have no relevant financial interest in this article.

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