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Giuseppina Marrazzo, Lars Bellner, Adna Halilovic, Michael W. Dunn, Michal L. Schwartzman; Corneal But Not Neutrophil Ho-2 Expression Contributes To Corneal Healing. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1996.
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Heme oxygenase (HO) is the rate-limiting enzyme in heme degradation. Our previous studies demonstrated that the HO system, in particular, the constitutive HO-2 is critical for a self resolving inflammatory and repair response. Epithelial injury in HO-2 null mice leads to impaired healing and chronic inflammation in the cornea. This study was undertaken to examine the possible relationship between HO-2 and the recruitment of inflammatory cells.
Re-epithelialization and neutrophil recruitment were assessed in wild type (WT) and HO-2 knockout (KO) mice treated with Gr-1 monoclonal antibody to deplete peripheral neutrophils. Re-epithelialization was measured by fluorescein staining. The number of inflammatory cells was visualized using H&E staining. Adhesion assay was performed using aortic endothelial cells (mAEC) from WT and KO mice and neutrophils isolated from WT mice. HO-1 and HO-2 expression was assessed by real-time PCR.
Wound closure in intact WT mice was 60% higher than in neutrophil-depleted WT mice and 85% higher in intact KO mice than neutrophil-depleted KO mice. H&E staining confirmed the lack of inflammatory cells in the cornea in neutrophil-depleted mice and showed that the number of neutrophils is markedly increased in corneas from HO-2 KO mice as compared to WT mice. WT neutrophils adhered more to mAEC KO cells than to WT. Real time PCR showed a significant difference in the HO-1expression between neutrophils purified from intact WT and neutrophil-depleted WT mice; no significant changes were observed in HO-1 expression in neutrophils of KO mice intact or neutrophil-depleted.
The HO-2 null mice showed an exaggerated corneal inflammation associated with increased number of inflammatory cells compared to WT. Our results demonstrated that the elevated number of neutrophils recruited to the injured tissues in HO-2 KO mice are not mainly responsible for the delay in healing, on the contrary, the lack of neutrophils, through depletion, increase significantly the delay in wound healing in both WT and KO.
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