| PURPOSE: Adhesion molecules play a critical role in leukocyte emigration to wound sites, but differences are evident in different vascular beds. In this study, the contributions of P-selectin to neutrophil emigration into the cornea after central epithelial abrasion were investigated. METHODS: Re-epithelialization, neutrophil influx, and platelet accumulation were assessed in C57BL/6 mice after removal of a 2-mm diameter area of central corneal epithelium that did not directly injure the limbal vessels or the avascular stroma of the cornea. Comparisons were made between wild-type (WT) mice and mice with targeted deletions of genes for P-selectin, CD18, or CD54, or mice with antibody-induced neutropenia or thrombocytopenia. RESULTS: After central corneal epithelial abrasion, platelets localized in the limbal vessels and neutrophils emigrated from the limbal vessels to the region of the epithelial wound. There was temporal correspondence of platelet and neutrophil localization, peaking within 12 hours of wounding. Platelet accumulation, neutrophil emigration and corneal epithelial healing as measured by wound closure, basal epithelial cell density, and epithelial cell division were significantly reduced in P-selectin-deficient mice (P-sel(-/-)). Anti-GP1balpha antibody-induced thrombocytopenia in WT mice significantly reduced platelet and neutrophil accumulation and wound healing. Passive transfer of wild-type platelets into P-sel(-/-) mice significantly restored platelet localization in limbal vessels, neutrophil emigration, epithelial cell division, and epithelial cell migration into the abraded region of the cornea. CONCLUSIONS: Platelet localization in the limbus of abraded corneas contributes to re-epithelialization, and P-selectin provides a necessary step in this process. |
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