title: The role of neutrophils in corneal wound healing in HO-2 null mice.
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-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-2(-/-) than in WT. However, the rate of corneal wound closure following neutrophil depletion was markedly inhibited in both WT and HO-2(-/-) mice by 60% and 85%, respectively. Neutropenia induced HO-1 expression in WT but not in HO-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 perturbation in endothelial cell function caused by HO-2 depletion underlies the increased infiltration of neutrophils into the HO-2(-/-) cornea. Moreover, the fact that neutropenia worsened epithelial healing of the injured cornea in both WT and HO-2(-/-) mice suggest that cells other than neutrophils contribute to the exaggerated inflammation and impaired wound healing seen in the HO-2 null cornea.
authors.affiliation: Department of Pharmacology and Ophthalmology, New York Medical College, Valhalla, New York, United States of America. giuseppina_marrazzo@nymc.edu
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Marrazzo
authors.forename: Lars
authors.initials: L
authors.lastname: Bellner
authors.forename: Adna
authors.initials: A
authors.lastname: Halilovic
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Michael W
authors.initials: MW
authors.lastname: Dunn
authors.forename: Michal Laniado
authors.initials: ML
authors.lastname: Schwartzman
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002452:Cell Count; D003315:Cornea / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D065306:Corneal Injuries; D042783:Endothelial Cells / Q000473:pathology; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency* / Q000235:genetics*; D051547:Heme Oxygenase-1 / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020556:Neutrophil Infiltration / Q000235:genetics; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000276:immunology*
chemical_list: D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2