A monoclonal antibody against human thrombospondin inhibits platelet aggregation

V. M. Dixit; D. M. Haverstick; K. M. O'Rourke; S. W. Hennessy; G. A. Grant; S. A. Santoro; W. A. Frazier

doi:10.1073/pnas.82.10.3472

A monoclonal antibody against human thrombospondin inhibits platelet aggregation

V. M. Dixit, D. M. Haverstick, K. M. O'Rourke, S. W. Hennessy, G. A. Grant, S. A. Santoro, W. A. Frazier

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122 Scopus citations

Abstract

A monoclonal antibody (C6.7) has been generated against the calcium-replete form of human platelet thrombospondin (TSP). C6.7 is specific for TSP as determined by both competitive radioimmunoassay and immunoprecipitation. This antibody inhibits both thrombin- and A23187-induced aggregation of gel-filtered platelets in a concentration-dependent manner without affecting the secretion of serotonin. The epitope on TSP recognized by C6.7 has been localized to an 18-kDa fragment that is present in mild chymotryptic digests of TSP. This fragment is disulfide-linked to a 120- to 140-kDa fragment in unreduced digests, and both reduction and denaturation are required to separate the 18-kDa peptide from the larger fragments. A 25-kDa heparin binding domain is also present in the chymotryptic digest. However, the 18-kDa peptide is distinct from the heparin binding domain. The amino acid sequence at the NH₂ terminus of the 18-kDa fragment is Asp-Thr-Asn-Pro-Thr-Arg-Ala-Gln-Gly-Tyr-.

Original language	English
Pages (from-to)	3472-3476
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	82
Issue number	10
DOIs	https://doi.org/10.1073/pnas.82.10.3472
State	Published - 1985

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title = "A monoclonal antibody against human thrombospondin inhibits platelet aggregation",

abstract = "A monoclonal antibody (C6.7) has been generated against the calcium-replete form of human platelet thrombospondin (TSP). C6.7 is specific for TSP as determined by both competitive radioimmunoassay and immunoprecipitation. This antibody inhibits both thrombin- and A23187-induced aggregation of gel-filtered platelets in a concentration-dependent manner without affecting the secretion of serotonin. The epitope on TSP recognized by C6.7 has been localized to an 18-kDa fragment that is present in mild chymotryptic digests of TSP. This fragment is disulfide-linked to a 120- to 140-kDa fragment in unreduced digests, and both reduction and denaturation are required to separate the 18-kDa peptide from the larger fragments. A 25-kDa heparin binding domain is also present in the chymotryptic digest. However, the 18-kDa peptide is distinct from the heparin binding domain. The amino acid sequence at the NH2 terminus of the 18-kDa fragment is Asp-Thr-Asn-Pro-Thr-Arg-Ala-Gln-Gly-Tyr-.",

author = "Dixit, {V. M.} and Haverstick, {D. M.} and O'Rourke, {K. M.} and Hennessy, {S. W.} and Grant, {G. A.} and Santoro, {S. A.} and Frazier, {W. A.}",

year = "1985",

doi = "10.1073/pnas.82.10.3472",

language = "English",

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T1 - A monoclonal antibody against human thrombospondin inhibits platelet aggregation

AU - Dixit, V. M.

AU - Haverstick, D. M.

AU - O'Rourke, K. M.

AU - Hennessy, S. W.

AU - Grant, G. A.

AU - Santoro, S. A.

AU - Frazier, W. A.

PY - 1985

Y1 - 1985

N2 - A monoclonal antibody (C6.7) has been generated against the calcium-replete form of human platelet thrombospondin (TSP). C6.7 is specific for TSP as determined by both competitive radioimmunoassay and immunoprecipitation. This antibody inhibits both thrombin- and A23187-induced aggregation of gel-filtered platelets in a concentration-dependent manner without affecting the secretion of serotonin. The epitope on TSP recognized by C6.7 has been localized to an 18-kDa fragment that is present in mild chymotryptic digests of TSP. This fragment is disulfide-linked to a 120- to 140-kDa fragment in unreduced digests, and both reduction and denaturation are required to separate the 18-kDa peptide from the larger fragments. A 25-kDa heparin binding domain is also present in the chymotryptic digest. However, the 18-kDa peptide is distinct from the heparin binding domain. The amino acid sequence at the NH2 terminus of the 18-kDa fragment is Asp-Thr-Asn-Pro-Thr-Arg-Ala-Gln-Gly-Tyr-.

AB - A monoclonal antibody (C6.7) has been generated against the calcium-replete form of human platelet thrombospondin (TSP). C6.7 is specific for TSP as determined by both competitive radioimmunoassay and immunoprecipitation. This antibody inhibits both thrombin- and A23187-induced aggregation of gel-filtered platelets in a concentration-dependent manner without affecting the secretion of serotonin. The epitope on TSP recognized by C6.7 has been localized to an 18-kDa fragment that is present in mild chymotryptic digests of TSP. This fragment is disulfide-linked to a 120- to 140-kDa fragment in unreduced digests, and both reduction and denaturation are required to separate the 18-kDa peptide from the larger fragments. A 25-kDa heparin binding domain is also present in the chymotryptic digest. However, the 18-kDa peptide is distinct from the heparin binding domain. The amino acid sequence at the NH2 terminus of the 18-kDa fragment is Asp-Thr-Asn-Pro-Thr-Arg-Ala-Gln-Gly-Tyr-.

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DO - 10.1073/pnas.82.10.3472

M3 - Article

C2 - 2582413

AN - SCOPUS:0021826587

SN - 0027-8424

VL - 82

SP - 3472

EP - 3476

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 10

ER -

A monoclonal antibody against human thrombospondin inhibits platelet aggregation

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