Altered expression of mast cell chymase and tryptase and of c-Kit in human cutaneous scar tissue.
In order to explore a possible involvement of mast cells during human wound healing, we studied sections from scars (4-369-d-old) (N = 20) and normal skin (N = 10) for mast-cell-specific tryptase and chymase by enzyme histochemistry, for the stem cell factor receptor c-Kit and the melanosomal marker TA99 by immunohistochemistry, and for simultaneous c-Kit expression and avidin fluorescence by double staining. Enzyme activities and mRNA expression were also studied in tissue extracts. Chymase-reactive mast cell numbers as well as chymase activity and mRNA expression were reduced in all scars, whereas overall numbers of tryptase-reactive cells did not differ from normal skin, although tryptase activity and mRNA expression were increased in scar extracts. In contrast, numbers of c-Kit positive cells were significantly increased in old scars, and in the mid and lower dermis of all scars. A marked reduction of c-Kit reactivity was noted, however, in avidin-positive dermal mast cells and in epidermal basal cells, despite unchanged numbers of melanosome-positive cells, with an associated overall decrease of c-Kit mRNA in scar extracts. These data thus show that numbers of resident mast cells are very low in human cutaneous scars, suggesting massive mediator release from these cells into fresh wounds. Downregulation of stem cell factor receptors may also prevent these cells from increasing in number even in old scars. Instead, scar tissue is populated by a mast cell subpopulation that is chymase-, avidin-, tryptase +, c-Kit +, reflecting most probably an increased immigration and/or proliferation of immature mast cells and their precursors.
Hermes
B
B
Department of Dermatology, Charité, Humboldt University, Berlin, Germany.
Feldmann-Böddeker
I
I
Welker
P
P
Algermissen
B
B
Steckelings
M U
MU
Grabbe
J
J
Henz
B M
BM
D053818:Chymases; D002921:Cicatrix / Q000201:enzymology*; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000378:metabolism*; D053802:Tryptases
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019009:Proto-Oncogene Proteins c-kit; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases