Role of wound macrophages in skin flap loss or survival in an experimental diabetes model.
BACKGROUND
Tightly controlled wound inflammation is a central determinant of skin flap survival in healthy mice. This study investigated inflammatory response patterns in caudally pedicled skin flaps in diabetic mice during severely impaired conditions of necrotic skin flap tissue loss.


METHODS
Skin flap biopsies were analysed by RNase protection assay, quantitative real-time polymerase chain reaction, immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting.


RESULTS
Skin flaps were characterized by the necrotic loss of tissue starting from distal areas of the flaps in diabetic mice. Decay of epidermal and dermal structures within skin flap tissue was paralleled by an immune cell-mediated expression of chemokines (macrophage inflammatory protein 2, macrophage chemoattractant protein 1), cyclo-oxygenase (COX) 2 and inducible nitric oxide synthase (iNOS). Distal regions of necrotic skin flap tissue were infiltrated by excess numbers of neutrophils and macrophages, and the latter were polarized towards a proinflammatory state as they expressed COX-2 and iNOS. Experimental depletion of inflammatory macrophages inhibited necrotic destruction of the distal skin flap tissue in diabetic mice despite the persistence of neutrophil infiltration and inflammation.


CONCLUSIONS
Wound macrophages play a pivotal role in determining the survival or loss of skin flap tissue under disturbed wound healing conditions in obese diabetic mice.
Schürmann
C
C
Pharmazentrum frankfurt/Centre for Drug Research, Development and Safety (ZAFES), Frankfurt am Main, Germany.
Seitz
O
O
Sader
R
R
Pfeilschifter
J
J
Goren
I
I
Frank
S
S
D000818:Animals; D001706:Biopsy; D018925:Chemokines / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000473:pathology*; D005260:Female; D006085:Graft Survival / Q000502:physiology; D007159:Immunologic Tests; D007249:Inflammation / Q000473:pathology*; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D012260:Ribonucleases / Q000378:metabolism; D013524:Surgical Flaps / Q000473:pathology*
D018925:Chemokines; D012313:RNA; D012260:Ribonucleases