Low recruitment of immune cells with increased expression of endothelial adhesion molecules in margins of the chronic diabetic foot ulcers.

Diabetic foot skin close to an ulcer shows only a few infiltrating cells compared to nondiabetic inflamed tissues. Diabetes is characterized by thickened basement membrane of the blood arterioles and capillaries. This may affect the transcapillary transport of immune humoral factors and cells to the extravascular space. We analyzed by immunohistochemistry the phenotype and expression pattern of adhesion molecules on leukocyte, dermal fibroblast, and endothelial cells in diabetic foot ulcers. Although there was accumulation of granulocytes on the surface and superficial layers of the granulation tissue, rare perivascular granulocyte infiltrates in the dermis were seen. Moreover, lack of macrophage and CD3+ T cell infiltrates was observed. In contrast, there was increased intensity of CD1a staining of Langerhans cells in the epidermis and papillary dermis (p < 0.05). Fibroblasts revealed increased presence in the ulcer margins compared with normal skin (p < 0.05). Skin endothelial cells expressed stronger von Willebrand factor and E-selectin compared with normal skin (p < 0.05). Our study provides evidence that increased expression of endothelial cell adhesion molecules responsible for immunocyte extravasation is not associated with increased inflammatory cell infiltration of the ulcerated diabetic foot tissue. We suggest that the healing process of diabetic foot ulcers may be hampered by mechanisms decreasing accumulation of leukocytes. This implies that pharmacological or biological stimulation of leukocyte extravasation into the ulcer tissue should be tried.