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 cytokine involved in both normal wound healing and scarring. We show that human platelets contain two pools of latent TGF-beta 1, which constitute more than 95% of the total TGF-beta assayed in whole platelets. During clotting, one pool, the large latent TGF-beta complex consisting of latent TGF-beta binding protein (LTBP), the latency-associated peptide (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 dissolved by plasmin this bound TGF-beta 1 is gradually activated and released. If similar mechanisms operate in vivo, the clot will act as a slow-release capsule of TGF-beta 1 activity during wound healing.
Grainger
D J
DJ
Department of Biochemistry, University of Cambridge, UK.
Wakefield
L
L
Bethell
H W
HW
Farndale
R W
RW
Metcalfe
J C
JC
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D002451:Cell Compartmentation; D005341:Fibrinolysin / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D046911:Macromolecular Substances; D009842:Oligopeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D011506:Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C047981:arginyl-glycyl-aspartic acid; C046617:arginyl-glycyl-aspartyl-serine; D013917:Thrombin; D005341:Fibrinolysin