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The stimulation of fibroblast proliferation by thrombin and factor XIII is accompanied by an intracellular increase of cGMP. In contrast fibronectin inhibits the 3H-thymidine uptake of fibroblasts. Pre-treatment of fibroblasts with neuraminidase eliminates the stimulating effect of thrombin completely and induces a shift of the optimum stimulating effect of factor XIII to higher concentrations. It is discussed that thrombin and factor XIII stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibroblasts in thrombus organization, wound healing and in the arteriosclerotic vessel wall process.

Skin fibroblast cultures were treated with various components of the blood clotting system (thrombin, fibrinogen and fibrin) during the logarithmic growth phase. Fibrin as well as thrombin showed dose-dependent growth promoting activities as revealed by cell counting and 3H-thymidine uptake. No effect was seen with fibrinogen. After entrapping in polymerizing fibrin enriched by complete culture medium the cells elongated, multiplied and formed net-like interconnecting cell strands throughout the clots. Nutritional deprivation appeared as a limiting factor for eventual growth cessation. The results demonstrate active growth of fibroblasts in fibrin clots such as present in healing wounds and thrombi. The production of thrombin by the coagulation cascade does not only result in the conversion of fibrinogen to fibrin but has also a long-lasting hormone-like effect on fibroblast proliferation which is of essential importance in wound healing, thrombus organization and progression of chronic atherosclerotic lesions.

Cultured skin fibroblasts from young male guinea pigs were irradiated with UVA light in the presence of 8-methoxypsoralen (8-MOP) or angelicin. As compared to 8-MOP 30 times higher concentrations of angelicin were needed to obtain comparative inhibition rates of DNA-synthesis. Complete cellular recovery could be observed when the cell cultures were treated with angelicin-plus-UVA (320-400 nm) or 8-MOP-plus-395 nm. Both treatment schedules are known to cause monofunctional photoreactions. In contrast to this, bifunctional photoreactions caused by 8-MOP-plus-365 nm produced an inhibition of DNA synthesis which lasted more than four days. Also, UVA (320-400 nm) applied to cells treated with 3H-labeled 8-MOP resulted in a dose-dependent binding of 8-MOP molecules again lasting several days. Application of 8-MOP-plus-UVA (320-400 nm) to cells growing in log-phase showed a characteristic change in morphology. An increasing number of polynuclear and hyperchromatic cells appeared with time after treatment. In this subpopulation of cells DNA synthesis continued without division as revealed by DNA measurements and autoradiography. It is concluded that monofunctional adducts caused by angelicin-plus-UVA as well as 8-MOP-plus-395 nm permit cellular recovery whereas bifunctional photoadducts remained without recovery. In the latter case semiconservative DNA synthesis continued leading to hyperchromatic cells which could serve as a parameter for the presence of cross-linked nuclear DNA strands.

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