Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function

There is increasing evidence that sensory nerves may participate in cutaneo us inflammatory responses by the release of neuropeptides such as substance P (SP). We examined the direct effect of SP on human dermal microvascular endothelial cell (HDMEC) intercellular adhesion molecule 1 (ICAM-1) express ion and function. Our results indicated that, although cultured HDMEC expre ssed mRNA for neurokinin receptors 1, 2, and 3 (NK-1R, NK-2R, and NK-SR), S P initiated a rapid increase in HDMEC intracellular Ca2+ levels, primarily by the activation of NK-1R. Immunohistochemistry studies likewise demonstra ted that HDMEC predominantly expressed NK-1R. The addition of SP to HDMEC r esulted in a rapid increase in cellular ICAM-1 mRNA levels, followed by a f ivefold increase in ICAM-1 cell surface expression. This functionally resul ted in a threefold increase in Cr-51-labeled binding of J-Y lymphoblastoid cells to HDMEC. In vivo studies demonstrated a marked increase in microvasc ular ICAM-1 immunostaining 24 and 48 h after application of capsaicin to th e skin. These results indicate that neuropeptides such as SP are capable of directly activating HDMEC to express increased levels of functional ICAM-1 and further support the role of the cutaneous neurological system in modul ating inflammatory processes in the skin.