RELEASE AND ACTIVATION OF PLATELET LATENT TGF-BETA IN BLOOD-CLOTS DURING DISSOLUTION WITH PLASMIN

Transforming growth factor beta 1 (TGF-beta 1) is a platelet-derived c ytokine involved in both normal wound healing and scarring. We show th at human platelets contain two pools of latent TGF-beta 1, which const itute more than 95% of the total TGF-beta assayed in whole platelets. During clotting, one pool, the large latent TGF-beta complex consistin g of latent TGF-beta binding protein (LTBP), the latency-associated pe ptide (LAP) and the 25-kD mature TGF-beta 1 dimer is released into the serum. A second pool, which contains LAP but not LTBP, is retained in the clot, but can be released by RGD peptide. When the clot is dissol ved by plasmin this bound TGF-beta 1 is gradually activated and releas ed. if similar mechanisms operate in vivo, the clot will act as a slow -release capsule of TGF-beta 1 activity during wound healing.