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Publication : Heme oxygenase-2 deletion impairs macrophage function: implication in wound healing.

First Author  Bellner L Year  2015
Journal  FASEB J Volume  29
Issue  1 Pages  105-15
PubMed ID  25342128 Mgi Jnum  J:218017
Mgi Id  MGI:5616455 Doi  10.1096/fj.14-256503
Citation  Bellner L, et al. (2015) Heme oxygenase-2 deletion impairs macrophage function: implication in wound healing. FASEB J 29(1):105-15
abstractText  Heme oxygenase (HO)-2 deficiency impairs wound healing and exacerbates inflammation following injury. We examine the impact of HO-2 deficiency on macrophage function and the contribution of macrophage HO-2 to inflammatory and repair responses to injury. Corneal epithelial debridement was performed in control and macrophage-depleted HO-2(-/-) and wild-type (WT) mice and in bone marrow chimeras. Peritoneal macrophages were collected for determination of phagocytic activity and classically activated macrophage (M1)-alternatively activated macrophage (M2) polarization. Depletion of macrophages delayed corneal healing (13.2%) and increased neutrophil infiltration (54.1%) by day 4 in WT mice, whereas in HO-2(-/-) mice, it did not worsen the already impaired wound healing and exacerbated inflammation. HO-2(-/-) macrophages displayed an altered M1 phenotype with no significant expression of M2 or M2-like activated cells and a 31.3% reduction in phagocytic capacity that was restored by inducing HO-1 activity or supplementing biliverdin. Macrophage depletion had no effect, whereas adoptive transfer of WT bone marrow improved wound healing (34% on day 4) but did not resolve the exaggerated inflammatory response in HO-2(-/-) mice. These findings indicate that HO-2-deficient macrophages are dysfunctional and that macrophage HO-2 is required for proper macrophage function but is insufficient to correct the impaired healing of the HO-2(-/-) cornea, suggesting that corneal epithelial expression of HO-2 is a key to resolution and repair in wound healing.-Bellner, L., Marrazzo, G., van Rooijen, N., Dunn, M. W., Abraham, N. G., Schwartzman, M. L. Heme oxygenase-2 deletion impairs macrophage function: implication in wound healing.
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