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Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin.

C H Smith, J N Barker, R W Morris, D M MacDonald and T H Lee
J Immunol September 15, 1993, 151 (6) 3274-3282;
C H Smith
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J N Barker
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R W Morris
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D M MacDonald
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T H Lee
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Abstract

Inflammatory cell infiltrates and cell adhesion molecule expression have been examined in normal human skin after intradermal injection of sensory neuropeptides substance P (n = 6), vasoactive intestinal polypeptide (n = 6), and calcitonin gene-related peptide (n = 6) together with PBS as control (n = 4). Each neuropeptide induced rapid, time-dependent neutrophil influx into dermis, which was initially observed at 15 min and persisted for 8 h after injection. Increases in numbers of neutrophils with time after substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide were highly significant when compared with controls p < 0.005, p < 0.005, p < 0.005, respectively (analysis of variance). Substance P additionally induced marked eosinophilic accumulation at 4 and 8 h in four of six subjects. These changes paralleled rapid translocation of P-selectin from cytoplasmic Weibel-Palade granules to luminal membranes by 15 min, and significant up-regulation of E-selectin expression at 4 and 8 h. Increases in percentage of E-selectin positive vessels with respect to time after each neuropeptide were highly significant when compared with controls, p < 0.005, p < 0.005, p < 0.005 (ANOVA), respectively, and were significantly correlated with neutrophil infiltrates, r = 0.55, p < 0.001. VCAM-1 was not expressed, and constitutive ICAM-1 expression on dermal endothelium was unchanged at all time points examined (0-8 h). Induction of endothelial adhesion molecule expression by neuropeptides provides a mechanism for neutrophil accumulation in neurogenic inflammation. Substance P-induced eosinophil accumulation in the absence of VCAM-1 expression suggests that mechanisms distinct from VCAM-1/very late antigen-4 binding mediate selective tissue eosinophilia.

  • Copyright © 1993 by American Association of Immunologists

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The Journal of Immunology
Vol. 151, Issue 6
15 Sep 1993
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Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin.
C H Smith, J N Barker, R W Morris, D M MacDonald, T H Lee
The Journal of Immunology September 15, 1993, 151 (6) 3274-3282;

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Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin.
C H Smith, J N Barker, R W Morris, D M MacDonald, T H Lee
The Journal of Immunology September 15, 1993, 151 (6) 3274-3282;
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Print ISSN 0022-1767        Online ISSN 1550-6606