Expression of mast cell growth modulating and chemotactic factors and their receptors in human cutaneous scars.
In order to explore possible mechanisms involved in the previously documented turnover of mast cell subpopulations in human cutaneous scars, we have examined selected factors known to stimulate and/or modulate mast cell hyperplasia (SCF, NGF, TGFbeta1, GM-CSF) and their receptors in human cutaneous scar tissue. On immunohistochemistry, numbers of SCF- and TGFbeta1-positive cells were significantly increased in the epidermis and throughout the dermis in scars (n = 27) of varying ages (4-369 d old), compared with normal skin (n = 12). Furthermore, TRbetaRI, II, and the NGF-p75 receptors were significantly increased in the epidermis, TRbetaRI and NGF-TrkA throughout the dermis, and TRbetaRII, NGF-p75, and GM-CSFR only in the mid- and lower dermis of scars. NGF and GM-CSF expression was in contrast scarce and weak, with no differences between normal skin and scars. In tissue extracts, mRNA levels of SCF, TGFbeta1, TRbetaI and II, and both NGF-receptors, but not GM-CSFR, were significantly increased as well. TRbetaI and II were identified in up to 90% and 83%, respectively, of isolated normal skin mast cells on flow cytometry, and GM-CSFR and NGFR-p75 were identified on 70% and 73%, respectively, of avidin-positive normal mast cells on double immunofluorescence microscopy. As described before for the SCF receptor KIT, GM-CSFR and NGFR-p75 were partly or entirely downregulated on avidin-positive mast cells in scars. The marked upregulation of TGFbeta1, its type I and II receptors, and SCF suggest that these factors play a major role in the orchestration of mast cell increase in human cutaneous scars whereas the role of NGF and GM-CSF is less clear, despite the significant upregulation of their receptors.
Department of Dermatology, Neukölln Hospital, Koln, Germany.
B
B
Hermes
P
P
Welker
I
I
Feldmann-Böddeker
S
S
Krüger-Krasagakis
K
K
Hartmann
T
T
Zuberbier
B M
BM
Henz
D002455:Cell Division / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism*; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D012871:Skin Diseases / Q000378:metabolism* / Q000473:pathology; D019089:Stem Cell Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D002630:Chemotactic Factors; D006133:Growth Substances; D017978:Receptors, Growth Factor; D019089:Stem Cell Factor; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020932:Nerve Growth Factor