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-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 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)-1alpha/beta. 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.
Trautmann
A
A
Department of Dermatology, University of Würzburg, Würzburg, Germany.
Toksoy
A
A
Engelhardt
E
E
Bröcker
E B
EB
Gillitzer
R
R
D000328:Adult; D002452:Cell Count; D018932:Chemokine CCL2 / Q000032:analysis* / Q000235:genetics; D002633:Chemotaxis; D053818:Chymases; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018836:Inflammation Mediators / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis* / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D008857:Microscopy, Interference; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000032:analysis; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D053802:Tryptases; D014945:Wound Healing
D018932:Chemokine CCL2; D018836:Inflammation Mediators; D012333:RNA, Messenger; D015847:Interleukin-4; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases