Mast cell involvement in normal human skin wound healing: expression of monocyte chemoattractant protein-I is correlated with recruitment of mast cells which synthesize interleukin-4 in vivo

Mast cells (MCs) are known as key cells of immediate type hypersensitivity reactions. It has recently been shown that MCs regulate fibroblast prolifer ation by heterotypic cell-cell contact and secretion of interleukin-4 (IL-4 ) in vitro. It was therefore hypothesized that MCs may contribute to wound repair in vivo. Using immunohistology and in situ hybridization, the time c ourse of mast cell recruitment and the expression of MC-attractant chemokin es were analysed in a human skin wound-healing model, and the production of IL-4 by MCs in vice was investigated. The data obtained indicate that the five-fold increase of the tryptase + MCs at the fibrotic border of the woun d within the first 10 days is the result of increased recruitment/survival of MCs or MC precursors, but not of increased local proliferation. Recruitm ent of MCs is paralleled by the expression of monocyte chemoattractant prot ein-1 (MCP-1), but not by other chemokines such as RANTES (regulated on act ivation, normal T cell ex-pressed and secreted) and/or MIP (macrophage infl ammatory protein)-1 alpha l beta. Notably, 60-70% of MCs exhibited strong a nd selective IL-4 immunoreactivity, whereas other resident and passenger ce lls were rather quiescent. The data suggest that MC contribute significantl y to the cytokine network of wound repair via MC-derived IL-4 and stimulati on of fibroblast proliferation. Copyright (C) 2000 John Wiley & Sons, Ltd.