Calcitonin gene-related peptide and vascular endothelial growth factor are expressed in lesional but not uninvolved skin in chronic spontaneous urticaria

Clin Exp Allergy. 2014 Aug;44(8):1053-60. doi: 10.1111/cea.12348.

Abstract

Background: The mechanisms for producing weals in chronic spontaneous (idiopathic) urticaria (CSU) are incompletely understood. Leucocyte infiltration with vascular leakage and expression of the potent vasoactive agents' calcitonin gene-related peptide (CGRP) and vascular endothelial growth factor (VEGF) are features of late-phase allergic skin reactions, previously proposed as a model of CSU.

Objective: To measure CGRP and VEGF expression in lesional and non-lesional skin from CSU patients and to compare results with a control group.

Methods: Eight paired biopsies (one from 4-8 h spontaneous weals and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects and studied by immunohistochemistry and confocal microscopy.

Results: Lesional skin in CSU contained significantly more CGRP+ and VEGF+ cells than non-lesional skin. No significant differences were observed in CGRP and VEGF expression between non-lesional skin and controls. In lesional skin, VEGF and CGRP co-localised to UEA-1+ blood vessels. CGRP was also expressed by neutrophils and eosinophils and to a lesser extent by CD90(+) fibroblasts, mast cells, CD3(+) and CD68(+) cells. CGRP and VEGF expression was not related to the duration of disease.

Conclusion and clinical relevance: Increased expression of CGRP and VEGF in lesional, but not uninvolved, skin indicates that these potent vasoactive agents may play a role in wealing and tissue oedema in CSU so representing novel targets in therapy.

Keywords: CGRP; VEGF; chronic spontaneous urticaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Surface / metabolism
  • Biopsy
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / metabolism*
  • Chronic Disease
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Urticaria / genetics
  • Urticaria / immunology*
  • Urticaria / metabolism*
  • Urticaria / pathology
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antigens, Surface
  • Vascular Endothelial Growth Factor A
  • Calcitonin Gene-Related Peptide