Fibrin in fibroblast cultures--a metabolic study as a contribution to inflammation and tissue repair.

Embryonic rat fibroblasts were cultured in the presence of fibrin under fibrinolytic and fibrinostatic conditions both in proliferating and confluent stages. The proliferation rate, glucose consumption, glycosaminoglycan contents and distribution pattern were determined. Additionally the influence on rat fibroblast cultures of fibrinogen and its splitting products were reinvestigated. Basing on the experimental results and a literature survey the role of fibrin in chronic inflammation was emphasized. Experimental results: 1. First step of tissue injury was simulated by formation of fibrin above a confluent fibroblast monolayer. The small degree of fibrinolysis with the cultures was sufficient to prevent all metabolic changes except a decrease of sulfate incorporation (immediately reversibly injury). Inhibition of fibrinolysis resulted in a decrease of proliferation and HA contents additionally, but in an increase of total GAG concentration and SO4-GAG. This behaviour continued during the beginning of cell proliferation. 2. The following step of fibrin contraction, improvement of nutrient supply, and cell proliferation was artificially achieved by growing non-confluent cells on the preformed fibrin network. Fibrin enhanced the cell proliferation, total GAG concentration, HA, and the turnover of SO4-GAG (sulfate incorporation). In rapidly proliferating cultures no influence of anti-fibrinolytic agents was observed. 3. On the preformed, partially contracted fibrin the cells grew to confluence: a) Without inhibition of the fibrinolysis, the parameters of the fibrin-free controls were obtained; repair seems to be completed. b) When fibrinolysis was inhibited the cells continued proliferating apparently with a tendency of enhanced HA and decreased SO4-GAG (a stage of "chronic inflammation"). 4. Purified fibrin fractions as well as the supernatant of fibrin containing fibrinopeptides were shown to advance cell proliferation.