Mechanisms for Expression of Thrombospondin on the Platelet Cell Surface

Aiken, Martha L.; Ginsberg, Mark H.; Plow, Edward F.

doi:10.1055/s-2007-1003506

Cited by 24 publications

(7 citation statements)

References 34 publications

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“…When it is secreted from platelet ␣ granules, a significant portion of the TSP-1 becomes associated with the surface of stimulated platelets (30,31). We assessed basal and thrombinstimulated TSP-1 surface expression by FACS, using a TSPI-1 mAb that was verified to react equally with Asn-700 and Ser-700 TSP-1 and platelets from three Ser-700 and three Asn-700 donors.…”

Section: Resultsmentioning

confidence: 99%

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Narizhneva

Byers-Ward

Quinn

et al. 2004

Journal of Biological Chemistry

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A serine (Ser-700) amino acid rather than an asparagine (Asn-700) at residue 700 of thrombospondin-1 has been linked to an increased risk for development of premature, familial heart attacks. We now have identified both functional and structural differences between the Ser-700 and Asn-700 thrombospondin-1 variants. The Ser-700 variant increased the rate and extent of platelet aggregation and showed increased surface expression on platelets compared with the Asn-700 variant. These differences could be ascribed to an enhanced interaction of the Ser-700 variant with fibrinogen on the platelet surface and are consistent with a prothrombotic phenotype in Ser-700 individuals. The Ser-700 variant thrombospondin-1 was conformationally more labile than the Asn-700 variant as demonstrated by increased susceptibility to proteolytic digestion and enhanced susceptibility to unfolding by denaturants. These data suggest a potential molecular and cellular basis for a genetic risk factor associated with early onset myocardial infarction.

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Section: Resultsmentioning

confidence: 99%

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Narizhneva

Byers-Ward

Quinn

et al. 2004

Journal of Biological Chemistry

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“…It is known that some of the α‐granule constituents released by platelets on activation, such as TSP and fibrinogen, can then bind to the plasma membrane of activated platelets in a calcium‐dependent manner [19, 20]and are therefore associated with the particulate fraction of activated platelets. When platelet activation was repeated in the presence of 1 mM EDTA, which inhibits this binding, it was again the particulate fraction which caused the greatest increase in gelatinase production (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Before use, washed degranulated platelets were disrupted on ice by sonication. In some experiments, thrombin‐induced activation was performed in the presence of 1 mM EDTA, to avoid the divalent‐cation dependent‐fixation of the released factors on the membrane of degranulated platelets [19, 20].…”

Section: Methodsmentioning

confidence: 99%

Upregulation of MMP‐9 expression in MDA‐MB231 tumor cells by platelet granular membrane

1997

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The interaction between tumor cells and platelets facilitates the formation of metastasis in a way depending on the platelet aggregating ability of the tumor cell, but the mechanism remains to be elucidated. We have shown, by zymography and Western blot, that platelets greatly increased the secretion to the culture medium of MMP-9 by human mammary tumor cells MDA-MB231. This increase, which was dependent on protein synthesis, was caused by the platelet aggregates interacting with the tumor cells and not by the soluble factors released during platelet activation. Platelet subcellular fractionation allowed the localization of the inducing factor to the membrane fraction of the platelet granules, thus requiring platelet aggregation in order to become accessible on the platelet surface.

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“…HourdillØ et al [48] showed that surface-bound TSP1 was drastically decreased by EDTA. Quantitative studies, using monoclonal antibodies and purified I 125 -TSP1, showed about 1000 -2000 TSP1 molecules on resting platelets, independent of the presence of bivalent cations [49], but 14 000 -16 000 TSP1 molecules on the activated platelet surface for 70 -80 % dependent on bivalent cations [49,50]. Thus, at least two types of receptors seem to be involved in TSP1 binding on the surface of platelets: non-inducible and inducible TSP1 receptors.…”

Section: Presence Of Tsp1 On Plateletsmentioning

confidence: 97%

Thrombospondins: from structure to therapeutics

Bonnefoy

Moura

Hoylaerts

2008

Cell. Mol. Life Sci.

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Thrombospondin-1 (TSP1) is a multi-domain, multi-functional glycoprotein synthesized by many cells. Matricellular TSP1 modulates cell adhesion and proliferation. TSP1 is involved in angiogenesis, inflammation, wound healing and cancer. As a major platelet protein, for a long time it was postulated to control hemostasis via platelet aggregate stabilization. However, these in vitro findings have been questioned in the absence of corroborating clinical data and of obvious hemostatic defects in TSP1 gene-deficient mice.Yet, the past few years have provided indices to implicate TSP1 in hemostasis. In clinical studies, a correlation exists between a welldefined TSP1 polymorphism and a significant risk of myocardial infarction. At the same time, recent in vivo animal model data imply TSP1 in the multimer size control of von Willebrand factor, in smooth muscle cell regulation and in vascular perfusion. These findings shed new light on the role of TSP1 in hemostasis and prothrombotic vascular pathologies. (Part of a Multi-author Review).

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Mechanisms for Expression of Thrombospondin on the Platelet Cell Surface

Cited by 24 publications

References 34 publications

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

Upregulation of MMP‐9 expression in MDA‐MB231 tumor cells by platelet granular membrane

Thrombospondins: from structure to therapeutics

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