DISTRIBUTION OF TYPE-II TGF-BETA RECEPTOR IMMUNOREACTIVITY IN NORMAL AND IMPAIRED MURINE AND HUMAN WOUNDS

Cloning and sequencing of the Type II transforming growth factor-beta receptor (TGF-beta IIR) gene has permitted the preparation of a polycl onal anti-receptor antiserum. We have used this antiserum in an immuno cytochemical survey of normal-healing, human skin wounds and chronic v enous ulcers. In addition, the TGF-beta IIR distribution in a murine m odel of full-thickness dermal wounds whose healing is impaired by appl ication of a semi-occlusive, vapor-permeable dressing was compared to that seen in control wounds treated with recombinant transforming grow th factor-beta 2 (rTGF-beta 2). In unwounded human and murine skin, sp ecific staining for the Type II TGF-beta receptor was seen in normal h air follicle and appendageal epithelia, with minimal epidermal and der mal immunoreactivity. Shortly after wounding, keratinocytes of the mig rating epidermal tongue expressed TGF-beta IIR while increased stainin g was only noted several days later in dermal fibroblasts, inflammator y cells, and the neovasculature. Application of rTGF-beta 2 to dressin g-inhibited mouse wounds increased the TGF-beta IIR staining in these same cells in the areas of TGF-beta 2 augmented granulation tissue. Ve nous ulcer biopsies exhibited TGF-beta IIR staining in the suprabasal keratinocytes at the wound margins as well as in a variety of cells in the non-healing wound bed. Using PCNA and procollagen immunostains, t here appeared to be an inverse correlation between the expression of T GF-beta IIR immunoreactivity and PCNA labeling density in human wound epithelial cells, while fibroblasts with a proliferative or synthetic phenotype expressed increased TGF-beta IIR immunoreactivity.