Effects of thrombospondin on fibrin polymerization and structure.
Thrombospondin (TSP) is a trace protein in plasma but is released in high concentrations from alpha-granules of activated platelets during hemostasis. It binds to the platelet membrane and becomes incorporated into fibrin clots. A variety of approaches were taken to learn the effects of TSP on fibrin polymerization and structure. 125I-TSP and 125I-fibrinogen were used to study the effect of TSP concentration on the extent of TSP and fibrin incorporation. Turbidity at 600 nm was used to monitor the time course of polymerization. Wavelength dependence of the turbidity was used to calculate the mass to length ratio, fiber diameter, and fiber density of fibrin formed in the presence and absence of TSP. Morphologies of control and TSP-containing clots were examined by electron microscopy following critical point drying. The initial TSP concentration influenced the amount of TSP incorporated but did not alter the extent of fibrin polymerization. TSP, in a concentration-dependent manner, reduced the lag time to turbidity rise and caused formation of more numerous but thinner fibers. Except for their diameter, these fibers were identical to fibers of control fibrin in terms of density and morphology. It is proposed that TSP interacts with fibrin intermediates to accelerate fiber growth, perhaps by serving as a trifunctional branching unit during network formation. The properties of fibrin around aggregating platelets, therefore, may be influenced considerably by secreted TSP.
D001792:Blood Platelets / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D009391:Nephelometry and Turbidimetry; D011108:Polymers / Q000378:metabolism; D011487:Protein Conformation; D013917:Thrombin / Q000494:pharmacology; D019699:Thrombospondins; D013997:Time Factors
D006023:Glycoproteins; D011108:Polymers; D019699:Thrombospondins; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin