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 document ed turnover of mast cell subpopulations in human cutaneous scars, we have e xamined selected factors known to stimulate and/or modulate mast cell hyper plasia (SCF, NGF, TGF beta1, GM-CSF) and their receptors in human cutaneous scar tissue. On immunohistochemistry, numbers of SCF- and TGF beta1-positi ve cells were significantly increased in the epidermis and throughout the d ermis in scars (n = 27) of varying ages (4-369 d old), compared with normal skin (n = 12). Furthermore, TR beta RI, II, and the NGF-p75 receptors were significantly increased in the epidermis, TR beta RI and NGF-TrkA througho ut the dermis, and TR beta RII, NGF-p75, and GM-CSFR only in the mid- and l ower 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, TGF beta1, TR betaI and II, and both NGF-receptors, b ut not GM-CSFR, were significantly increased as well. TR betaI 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% a nd 73%, respectively, of avidin-positive normal mast cells on double immuno fluorescence microscopy. As described before for the SCF receptor KIT, GM-C SFR and NGFR-p75 were partly or entirely downregulated on avidin-positive m ast cells in scars. The marked upregulation of TGF beta1, its type I and II receptors, and SCF suggest that these factors play a major role in the orc hestration of mast cell increase in human cutaneous scars whereas the role of NGF and GM-CSF is less clear, despite the significant upregulation of th eir receptors.