Substance P and Calcitonin Gene-Related Peptide: Effects on Mast Cells and in Human Skin

Abstract

Mast cells are found in close association with blood vessels, and histamine is known to be a potent vasodilator in humans. It is now clear that mast cells form neuroeffector junctions and that one of the types of nerve involved is the peptide-containing primary afferent neurone (C fibre). Nerve stimulation produces vasodilation which is blocked by antihistamines or by depletion of mast cell histamine with compound 48/80. Nerve stimulation also releases histamine and degranulates mast cells. Substance P and other neuropeptides release histamine from isolated rat and human skin mast cells. The actions of substance P and calcitonin gene-related peptide in human skin are compatible with a role for these two peptides in neurogenic inflammation. The inflammatory effects of substance P in human skin are inhibited by antihistamines. The possible role of the mast cell in neurogenic inflammation is discussed.

Joint capsule mast cells and neuropeptides are increased within four weeks of injury and remain elevated in chronic stages of posttraumatic contractures

“…It has been well described that Substance P and CGRP can cause mast cell degranulation, and this is in part their contribution to neurogenic inflammation represented by pain and swelling. 8,11,13,14,17,18 In addition, the mast cell factors liberated can contribute to fibrosis as well. However, the extent of the changes was maximal after 4 weeks postinjury and one cannot make any interpretations regarding "cause and effect" relationships between the three components addressed in this study.…”

“…Sections of skin are sources of blood vessels (α-SMA), mast cells, and neuropeptide containing nerve fibers, and these positive controls tested appropriately in both species. 12,14,20 Negative controls included substituting primary antibodies with 3% bovine serum albumin.…”

“…9,12,15,16 It has been well described that the neuropeptides Substance P and CGRP can cause mast cell degranulation. 8,11,13,14,17,18 Peptidergic nerve terminalshavebeen detectedin close association with mast cells in skin, ligament, joint capsule, and the gut. 10,11,13,14,19 It was recently reported that both the density of Substance P positive fibers and the number of mast cells were increased in the pathologic palmar fascia of patients with Dupuytren's contracture when compared to nonpathologic palmar fascia of control individuals.…”

“…8,11,13,14,17,18 Peptidergic nerve terminalshavebeen detectedin close association with mast cells in skin, ligament, joint capsule, and the gut. 10,11,13,14,19 It was recently reported that both the density of Substance P positive fibers and the number of mast cells were increased in the pathologic palmar fascia of patients with Dupuytren's contracture when compared to nonpathologic palmar fascia of control individuals. 19 Thus, the myofibroblast-mast cell-neuropeptide pathway may represent what is abnormal (myofibroblasts), how this abnormality comes about (mast cell degranulation liberating growth factors), and why this may occur (neuropeptide induced degranulation of mast cells).…”

“…8 Mast cells are widely distributed throughout connective tissues, including skin and joint capsules. [8][9][10][11][12][13][14] Mast cell granules contain preformed mediators associated with fibrosis including platelet-derived growth factor-A, basic fibroblast growth factor and endothelin-1, while the profibrotic TGF-β 1 is formed upon mast cell stimulation. 9,12 It is generally believed that mast cells induce a fibrotic response via involvement of connective tissue fibroblasts and myofibroblasts.…”