We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Heme oxygenase-2 deletion impairs macrophage function: implication in wound healing.
- Authors
Bellner, Lars; Marrazzo, Giuseppina; van Rooijen, Nico; Dunn, Michael W.; Abraham, Nader G.; Schwartzman, Michal L.
- Abstract
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.
- Subjects
INFLAMMATION; HEME oxygenase; BONE marrow transplantation; MACROPHAGES; CHIMERISM
- Publication
FASEB Journal, 2015, Vol 29, Issue 1, p105
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.14-256503