title: Neuropeptides induce rapid expression of endothelial cell adhesion molecules and elicit granulocytic infiltration in human skin.
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.
authors.affiliation: Department of Public Health Medicine, United Medical School, London.
authors.forename: C H
authors.initials: CH
authors.lastname: Smith
authors.forename: J N
authors.initials: JN
authors.lastname: Barker
authors.forename: R W
authors.initials: RW
authors.lastname: Morris
authors.forename: D M
authors.initials: DM
authors.lastname: MacDonald
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
mesh_terms: D000328:Adult; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1; D009479:Neuropeptides / Q000494:pharmacology*; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D009479:Neuropeptides; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1