Growth factors for human pleural mesothelial cells in soluble products from formed clots.
Fibrin deposition within the pleural space may influence repair following pleural injury. Although the mesothelial surface can organize fibrin, 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 chains of fibrinogen to generate fibrin monomer. Since these peptides are mitogenic for human fibroblasts, we considered that they might stimulate replication of human pleural mesothelial cells (HPMC). Application of fluid expressed from fibrin clots significantly increased cell number and stimulated uptake of 3H-thymidine by HPMC compared with untreated cells. The mitogenic response of subconfluent HPMC to dilutions of clot fluid (30-150 micrograms/ml protein) was comparable to that of 0.1 nM TGF-beta. Fibrinopeptide A (7.5-30 microM) stimulated 3H-thymidine uptake in HPMC, but FPB had only a slight effect at 30 microM. Antibody to FPA antibody significantly attenuated the mitogenic effect of clot fluid, indicating that a major component is FPA. Our study suggests that fibrinopeptides released during fibrin formation in vivo may stimulate local mesothelial regeneration following pleural injury.
Griffith
D E
DE
Department of Medicine, University of Texas Health Center, Tyler 75710.
Johnson
A R
AR
Kumar
A
A
Holiday
D B
DB
Idell
S
S
D002384:Catalysis; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects; D005340:Fibrinogen / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D010994:Pleura / Q000187:drug effects* / Q000502:physiology; D012995:Solubility; D013917:Thrombin / Q000502:physiology
D006133:Growth Substances; D008934:Mitogens; D005340:Fibrinogen; D013917:Thrombin