Divergent effects of the major mast cell products histamine, tryptase and TNF-alpha on human fibroblast behaviour

Abstract

Fibroblast proliferation is a key process in tissue remodeling and mast cells (MCs) are thought to play a crucial role. Having established that the three major MC products, tryptase, histamine and TNF-alpha (TNF) are normally present in human skin MCs, which are in close proximity to dermal fibroblasts, we studied their individual effects on cell cycle-controlled human dermal fibroblasts (HFFF2). These cells express receptors (H1, PAR2, TNFR1/2) for the major MC mediators, but only tryptase or a PAR2 agonist peptide stimulated proliferation and gene expression. TNF was antimitotic, and histamine, while elevating intracellular Ca2+ levels at high concentrations, did not affect proliferation. We conclude that MC products but also composition and numbers of respective receptors on fibroblasts are crucially responsible for fibroproliferative events.

Cardiac Mast Cells Mediate Left Ventricular Fibrosis in the Hypertensive Rat Heart

“…Likely, this concentration represents the high end of the concentration response to tryptase by these cells, and, as such, low levels of tryptase induce collagen synthesis, whereas higher levels are required for fibroblast proliferation in the SHR. Tryptase is known to induce proliferation of human fetal dermal fibroblasts, 18 and induction of collagen synthesis by tryptase has been demonstrated in human skin 19 and lung fibroblasts 20 ; however, this is the first study to demonstrate tryptase-induced modulation of adult cardiac fibroblasts, identifying this as a likely mechanism contributing to mast cell-mediated LV fibrosis.…”

The Importance of Mast Cells in Dermal Scarring

“…Tryptase has chemotactic and mitogenic effects on fibroblasts and also stimulates collagen synthesis, contraction, and differentiation into myofibroblasts. 70,73,74 Part of these effects may be due to the ability of mast cell histamine and tryptase to stimulate the production of FGF-2 and FGF-7 by fibroblasts. 75 Another mast cell protease, chymase, has been shown in vitro to cleave procollagen type I and promote collagen fibril formation directly.…”

Microsurgical Extrahepatic Cholestasis in the Rat: A Histopathological Liver Study

“…Interactions between mast cells and fibroblasts are paramount in the genesis of fibrosis [36,37]. It has been demonstrated that mast cells can communicate with fibroblast in a manner that leads to fibroblast activation and subsequent modulation of some aspects of extracellular fibrosis [37,38].…”

“…It has been demonstrated that mast cells can communicate with fibroblast in a manner that leads to fibroblast activation and subsequent modulation of some aspects of extracellular fibrosis [37,38]. However, the results of a study using mast cell-deficient Ws/Ws rats suggested that an increase of mast cells in the liver may be associated with fibrosis, but was not a cause of fibrosis [39].…”