Thrombospondin peptides inhibit the secretion-dependent phase of platelet aggregation.
Thrombospondin (TSP) is a platelet alpha-granule adhesive glycoprotein (M(r) = 450,000) that is released in large amounts from activated platelets and participates in thrombus formation. The aim of the present study was to assess the effect of peptides corresponding to sequences within the NH2-terminal region and type 1 repeats of TSP on platelet aggregation induced by thrombin in washed platelet suspensions. We found that TSP18 (amino acids 1-174), used at micromolar concentrations, inhibited platelet aggregation by 30-50%, reducing the size of the aggregates formed. Similar results were obtained with the hexapeptide Cys-Ser-Val-Thr-Cys-Gly (amino acids 429-434 and 486-491) used at 1.2 mM. The shorter peptide Val-Thr-Cys-Gly was even more inhibitory whereas the peptide Val-Thr-Lys-Gly, which lacks a cysteine, had no effect. Interestingly, we have constantly found that inhibition of platelet aggregation by these peptides was accompanied by an inhibition of alpha and dense granule secretion, suggesting that the binding of secreted TSP to the plasma membrane may participate in the platelet signaling process. We conclude that peptides of TSP may prove useful in the treatment of thrombosis by impairing both the release of proaggregating substances and platelet macroaggregate formation.
Rabhi-Sabile
S
S
Unité 353 INSERM, Paris, France.
Thibert
V
V
Legrand
C
C
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D019699:Thrombospondins
D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D019699:Thrombospondins