Expression of E- and P-selectin in tumor necrosis factor-induced dermatitis in dogs

Adhesion molecules on endothelial cells play an important role in leukocyte recruitment in several inflammatory processes. Vascular selectins mediate the initial adhesion of leukocytes to the blood vessel wall during their extravasation into inflamed tissues, and in vitro studies in dogs have shown that selectin expression can be induced by cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-l (IL-1). The objective of this study was to determine whether vascular selectins are induced by cytokines in vivo in a cutaneous model of inflammation in dogs. Skin biopsies were collected from nine dogs at various time points after an intradermal injection of TNF-alpha (10 ng/site) or phosphate-buffered saline containing 0.1% bovine serum albumin, and immunohistochemistry was performed using anti-P-selectin (MD3) and anti-E-selectin (CL37) monoclonal antibodies. In all animals, TNF-alpha induced an inflammatory reaction that was maximal at 12 hours and then decreased by 24 and 48 hours. Control skin displayed no expression of E- and P-selectin, whereas TNF-alpha induced the expression of P-selectin and E-selectin on dermal vessels that was highest at 12 hours and 3 hours, respectively (P < 0.05). Numerous platelet aggregates recognized by the anti-P-selectin antibody were present in the lumina of vessels anti in perivascular tissues. These results demonstrate that TNF-<alpha> can induce the expression of P- and E-selectin in vivo in dog skin and suggest that these selectins are involved in leukocyte recruitment in canine dermatitis.