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Am J Physiol Cell Physiol 275: C1580-C1590, 1998;
0363-6143/98 $5.00
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Vol. 275, Issue 6, C1580-C1590, December 1998

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

Kimberly L. Quinlan1, In-Sung Song1, Nigel W. Bunnett2, Eleanor Letran3, Martin Steinhoff2, Brad Harten1, John E. Olerud3, Cheryl A. Armstrong1,4, S. Wright Caughman1, and John C. Ansel1,4

1 Department of Dermatology and Emory Skin Diseases Research Core Center, Emory University School of Medicine and 4 Department of Veterans Affairs Medical Center, Atlanta, Georgia 30322; 2 Departments of Physiology and Surgery, University of California, San Francisco, California 94140; and 3 Department of Dermatology, University of Washington, Seattle, Washington 98195

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 Ca2+ 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 51Cr-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.

intercellular adhesion molecule 1; cell surface molecules; neuroimmunology; inflammation; skin


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