GROWTH-FACTORS, TISSUE AND UROKINASE-TYPE PLASMINOGEN ACTIVATORS IN VENOUS ULCERS

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 unheated (p=0.036, Mann-Whitney U-test). The results show that the predominant plasminogen activator in venous ulceration is u-pA, and that plasminogen activator inhibitors have little activity in venous ulceration. The bulk of TGF-beta(1) in venous ulcers is bound to latency-associated proteins, TGF-beta(1) and bFGF may have greater roles in venous ulceration than PDGF. Though there are greater concentrations of growth factors in venous ulcer bases, ulcer healing may relate more closely to growth factors present in the edge of the ulcer.