Release and activation of platelet latent TGF− in blood clots during dissolution with plasmin

Transforming growth factor 1 (TGF−1) is a platelet−derived cytokine involved in both normal wound healing and scarring. We show that human platelets contain two pools of latent TGF−1, which constitute more than 95% of the total TGF− assayed in whole platelets. During clotting, one pool, the large latent TGF− complex consisting of latent TGF− binding protein (LTBP), the latency−associated peptide (LAP) and the 25−kD mature TGF−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 dissolved by plasmin this bound TGF−1 is gradually activated and released. If similar mechanisms operate in vivo, the clot will act as a slow−release capsule of TGF−1 activity during wound healing.

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