Growth factors, tissue and urokinase-type plasminogen activators in venous ulcers.
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Bioimmunoassays for tissue and urokinase-type plasminogen activators (t-pA and u-pA), and enzyme-linked immunosorbent assays (ELISA) for t-pA were performed on biopsies from the edge and base of 15 venous ulcers. TGF-beta 1, bFGF and PDGF were assessed by ELISA in the edge and base of 19 further venous ulcers and 7 biopsies of normal skin. The presence of all three growth factors and u-pA was confirmed immunohistochemically. T-pA was detected using the ELISA and the bioimmunoassay, but was quantified in 3/15 ulcer bases and 4/15 ulcer edges using the bioimmunoassay only. U-pA was measured in all ulcer samples except one. TGF-beta 1 was measured in 13/19 ulcer bases and 9/19 edges, while free TGF-beta 1 was measured in only 2/19 bases and 4/19 edges. Venous ulcer bases contain significantly greater quantities of u-pA, TGF-beta 1, and bFGF than ulcer edges. TGF-beta 1 was never detected in normal skin. There is significantly less bFGF in normal skin than in venous ulcer bases, but not edges (p = 0.013, p = 0.31 respectively, Mann Whitney U-test). There was a good correlation between ulcer edge TGF-beta 1 and time to healing in ten ulcers that healed within six months from the date of biopsy (r = -0.56, p = 0.065, Spearman Rank Correlation). There was a significantly greater amount of ulcer edge bFGF in the ulcers that healed within six months than those that remained unhealed (p = 0.036, Mann-Whitney U-test).(ABSTRACT TRUNCATED AT 250 WORDS)