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PMID: 6501568 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Role of thrombospondin in platelet aggregation.

The Journal of clinical investigation ·Vol. 74 ·No. 5 ·1984-11-00 ·Pages 1764-72

Leung LL

Abstract

Thrombospondin (TSP), the major alpha-granule protein of human platelets, binds to the activated platelet surface upon platelet stimulation. TSP has hemagglutinating (lectin-like) activity and forms a specific complex with fibrinogen. Based on these observations, it was postulated that the interaction of TSP and fibrinogen on the activated platelet surface may be an important step in the platelet aggregation process. To test this hypothesis, monospecific, affinity-purified anti-TSP Fab fragments were prepared and their effects on platelet aggregation and platelet fibrinogen binding were studied. Anti-TSP Fab caused significant interference with thrombin- and collagen-induced platelet aggregation, as monitored by both turbidometric aggregometry and particle counting measuring the disappearance of single platelets. Phase-contrast microscopy revealed that anti-TSP Fab caused a marked decrease in platelet macroaggregates and an increase in microaggregates and nonaggregated single platelets. Anti-TSP Fab did not affect the initial phase of ADP-induced platelet aggregation but caused rapid platelet disaggregation with the abolition of the secondary phase of aggregation. The effect of anti-TSP Fab was not mediated by a direct inhibition of platelet secretion. The effect of anti-TSP Fab on specific binding of labeled fibrinogen to thrombin-stimulated platelets was also studied. Anti-TSP Fab caused a marked decrease in the affinity of fibrinogen binding to the receptors on the activated platelet surface. Kinetic analyses revealed significant displacement of labeled fibrinogen by unlabeled fibrinogen in the presence of anti-TSP Fab, suggesting that TSP serves to stabilize fibrinogen binding to the activated platelet surface and reinforces the strength of interplatelet interactions. It is proposed that platelet aggregation is a dynamic, multistep process, governed initially by the platelet membrane glycoprotein IIb/IIIa-fibrinogen interaction, with the TSP-fibrinogen interaction playing an important role in determining the size and reversibility of platelet aggregates.

MeSH Terms
Adenosine Diphosphate/pharmacology Antigen-Antibody Reactions Blood Platelets/physiology Collagen/pharmacology Fibrinogen/metabolism Glycoproteins/physiology Humans Immunoglobulin Fab Fragments Kinetics Platelet Aggregation/drug effects Thrombin/pharmacology Thrombospondins
Chemicals
Glycoproteins Immunoglobulin Fab Fragments Thrombospondins Adenosine Diphosphate Fibrinogen Collagen Thrombin
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Leung L L
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53 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI111595
Published
1984-11-00
Pages
1764-72
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC425356
Subset
IM
Grants
NHLBI NIH HHS · K08 HL00877 · United States
External Links
PubMed source DOI: 10.1172/JCI111595 PMC Full Text View journal details
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