the role of neutrophils in corneal wound healing in ho-2 null mice中性粒细胞的作用在ho-2空小鼠角膜伤口愈合.pdfVIP

The Role of Neutrophils in Corneal Wound Healing in HO-2 Null Mice 1,2 1 1 2 3 Giuseppina Marrazzo *, Lars Bellner , Adna Halilovic , Giovanni Li Volti , Filippo Drago , Michael W. 1 1 Dunn , Michal Laniado Schwartzman * 1 Department of Pharmacology and Ophthalmology, New York Medical College, Valhalla, New York, United States of America, 2 Department of Drug Sciences Section of Biochemistry, University of Catania, Catania, Italy, 3 Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy Abstract Our studies demonstrated that Heme oxygenase (HO), in particular, the constitutive HO-2, is critical for a self-resolving inflammatory and repair response in the cornea. Epithelial injury in HO-2 null mice leads to impaired wound closure and chronic inflammation in the cornea. This study was undertaken to examine the possible relationship between HO-2 and the recruitment of neutrophils following a corneal surface injury in wild type (WT) and HO-2 knockout (HO-22/ 2) mice treated with Gr-1 monoclonal antibody to deplete peripheral neutrophils. Epithelial injury was performed by removing the entire corneal epithelium. Infiltration of inflammatory cell into the cornea in response to injury was higher in HO-22/ 2 than in WT. However, the rate of corneal wound closure following neutrophil depletion was markedly inhibited in both WT and HO-22/ 2 mice by 60% and 85%, respectively. Neutropenia induced HO-1 expression in WT but not in HO-22/ 2 mice. Moreover, endothelial cells lacking HO-2 expressed higher levels of the Midkine and VE-cadherin and displayed strong adhesion to neutrophils suggesting that pe