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

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)C1580-C1590
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number6 44-6
DOIs
StatePublished - 1998

Keywords

  • Cell surface molecules
  • Inflammation
  • Intercellular adhesion molecule 1
  • Neuroimmunology
  • Skin

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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    Quinlan, K. L., Song, I. S., Bunnett, N. W., Letran, E., Steinhoff, M., Harten, B., Olerud, J. E., Armstrong, C. A., Wright Caughman, S., & Ansel, J. C. (1998). Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function. American Journal of Physiology - Cell Physiology, 275(6 44-6), C1580-C1590. https://doi.org/10.1152/ajpcell.1998.275.6.c1580