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

1998; American Physical Society; Volume: 275; Issue: 6 Linguagem: Inglês

10.1152/ajpcell.1998.275.6.c1580

1522-1563

Kimberly L. Quinlan, In-Sung Song, Nigel W. Bunnett, Eleanor L. Letran, Martin Steinhoff, Brad Harten, John E. Olerud, Cheryl A. Armstrong, S. Wright Caughman, John C. Ansel,

Cancer, Stress, Anesthesia, and Immune Response

There is increasing evidence that sensory nerves may participate in cutaneous 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) expression and function. Our results indicated that, although cultured HDMEC expressed mRNA for neurokinin receptors 1, 2, and 3 (NK-1R, NK-2R, and NK-3R), SP initiated a rapid increase in HDMEC intracellular Ca 2+ levels, primarily by the activation of NK-1R. Immunohistochemistry studies likewise demonstrated that HDMEC predominantly expressed NK-1R. The addition of SP to HDMEC resulted in a rapid increase in cellular ICAM-1 mRNA levels, followed by a fivefold increase in ICAM-1 cell surface expression. This functionally resulted in a threefold increase in 51 Cr-labeled binding of J-Y lymphoblastoid cells to HDMEC. In vivo studies demonstrated a marked increase in microvascular ICAM-1 immunostaining 24 and 48 h after application of capsaicin to the 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 modulating inflammatory processes in the skin.