VENOUS ULCER FIBROBLASTS COMPARED WITH NORMAL FIBROBLASTS SHOW DIFFERENCES IN COLLAGEN BUT NOT FIBRONECTIN PRODUCTION UNDER BOTH NORMAL ANDHYPOXIC CONDITIONS

Previous immunocytochemical analysis showed that the base of venous ul cers was deficient in fibronectin compared with surrounding ''normal'' dermis. Here, we investigate whether impaired synthetic ability of ul cer fibroblasts could underlie this observation, Ulcer fibroblasts, es tablished in culture from biopsies of the edge of chronic venous leg u lcers, were compared with normal fibroblasts grown from biopsies of si te- and age-matched normal skin for their ability to synthesize matrix molecules, Collagen and fibronectin synthesis were measured following metabolic labeling, as collagenase susceptible counts and counts with gelatin affinity, respectively. More collagen was produced by normal fibroblasts than ulcer fibroblasts, both when the cells were cultured on plastic and in collagen gels. In fibronectin synthesis, however, th ere was no major difference between the two cell types on either subst ratum, The hypoxic environment to which ulcer fibroblasts are exposed may have caused the intrinsic differences in collagen synthesis by the two fibroblast types. When we tested the effect of culturing cells un der hypoxic conditions, both cell types produced less collagen, especi ally normal fibroblasts grown in a collagen gel, but there was no effe ct of hypoxia on fibronectin synthesis. We conclude that venous ulcer edge-derived fibroblasts have an impaired ability to synthesize collag en in vitro, but synthesize fibronectin normally. Therefore, the low l evel of fibronectin found in venous ulcers is not likely to be due to the inability of ulcer cells to produce it or to the response to hypox ic conditions but may be due to the degradation of synthesized fibrone ctin by proteases present in these ulcers.