Mast cell involvement in normal human skin wound healing: expression of monocyte chemoattractant protein-1 is correlated with recruitment of mast cells which synthesize interleukin-4in vivo

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Abstract
Mast cells (MCs) are known as key cells of immediate type hypersensitivity reactions. It has recently been shown that MCs regulate fibroblast proliferation 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 course of mast cell recruitment and the expression of MC‐attractant chemokines were analysed in a human skin wound‐healing model, and the production of IL‐4 by MCs in vivo was investigated. The data obtained indicate that the five‐fold increase of the tryptase+ MCs at the fibrotic border of the wound within the first 10 days is the result of increased recruitment/survival of MCs or MC precursors, but not of increased local proliferation. Recruitment of MCs is paralleled by the expression of monocyte chemoattractant protein‐1 (MCP‐1), but not by other chemokines such as RANTES (regulated on activation, normal T cell expressed and secreted) and/or MIP (macrophage inflammatory protein)‐1α/β. Notably, 60–70% of MCs exhibited strong and selective IL‐4 immunoreactivity, whereas other resident and passenger cells were rather quiescent. The data suggest that MC contribute significantly to the cytokine network of wound repair via MC‐derived IL‐4 and stimulation of fibroblast proliferation. Copyright © 2000 John Wiley & Sons, Ltd.