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Macrophage Dysfunction and Impaired Wound Healing in Corneas of Heme Oxygenase (HO)‐2 Deficient Mice
Author(s) -
Bellner Lars,
Marrazzo Giuseppina,
Castellano Kirkland,
Dunn Michael W,
Schwartzman Michal L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.649.10
Subject(s) - wound healing , inflammation , heme oxygenase , neovascularization , corneal epithelium , macrophage , cornea , chemistry , andrology , heme , immunology , medicine , microbiology and biotechnology , biology , ophthalmology , angiogenesis , biochemistry , in vitro , enzyme
Corneal epithelial injury in HO‐2 null (KO) mice leads to delayed wound healing, exaggerated inflammatory cell infiltration, unresolved inflammation, ulceration, perforation and neovascularization. We examined the effect of systemic macrophage (MØ) depletion, using clodronate liposomes, on corneal wound healing in WT and KO mice. The corneal epithelium was removed in control and MØ‐depleted WT and KO mice. MØ depletion of WT mice delayed corneal wound healing when compared with the control group by 15% at day 4 after injury (p<0.05). Surprisingly, MØ depletion of KO mice had no additional effect on an already impaired corneal wound healing. Furthermore, MØ depletion caused a 100% (p<0.05) increase in the number of PMNs in the corneas of WT mice, whereas no significant change in the number of accumulating PMNs was observed in the corneas of KO mice. HO‐2 silencing of RAW 264.7 MØ using HO‐2 shRNA reduced phagocytic capacity by 40% (p<0.05), whereas HO‐induction using SnCl 2 increased phagocytic capacity by 85% (p<0.05). Together these data indicate that HO‐2 deletion impairs MØ function and that an intact HO‐2 is required for ordered inflammatory and repair response. Supported in part by NIH grant EY06513 (MLS).