GROWTH-FACTORS FOR HUMAN PLEURAL MESOTHELIAL CELLS IN SOLUBLE PRODUCTS FROM FORMED CLOTS

Fibrin deposition within the pleural space may influence repair follow ing pleural injury. Although the mesothelial surface can organize fibr in, the contribution of pleural mesothelial cells to pleural repair is unknown. During coagulation thrombin cleaves Fibrinopeptide A (FPA, A alpha 1-16) and fibrinopeptide B (FPB) from the A alpha and B beta ch ains of fibrinogen to generate fibrin monomer. Since these peptides ar e mitogenic for human fibroblasts, we considered that they might stimu late replication of human pleural mesothelial cells (HPMC). Applicatio n of fluid expressed from fibrin clots significantly increased cell nu mber and stimulated uptake of H-3-thymidine by HPMC compared with untr eated cells. The mitogenic response of subconfluent HPMC to dilutions of clot fluid (30-150 mu g/ml protein) was comparable to that of 0.1 n M TGF-beta. Fibrinopeptide A (7.5-30 mu M) stimulated H-3-thymidine up take in HPMC, but FPB had only a slight effect at 30 mu M. Antibody to FPA antibody significantly attenuated the mitogenic effect of clot fl uid, indicating that a major component is FPA. Our study suggests that fibrinopeptides released during fibrin formation in vivo may stimulat e local mesothelial regeneration following pleural injury.