Characterization of a chondroitin 4-sulfate proteoglycan carrier for heparin neutralizing activity (platelet factor 4) released from human blood platelets☆

Barber, A.J.; Käser-Glanzmann, R.; Jakábová, Milica; Lüscher, E. F.

doi:10.1016/0304-4165(72)90267-x

Cited by 176 publications

(78 citation statements)

References 21 publications

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“…21 Both CS and heparin are sulfated GAGs that carry a net negative charge; however, CS carries fewer than half as many sulfates as heparin (0.97 vs 2.33 sulfates per disaccharide subunit, respectively). 29 Consistent with this difference, the avidity of heparin for PF4 is much greater than that of CS. 29 A commonly used diagnostic maneuver to confirm the specificity of antibodies that test positive in the PF4 ELISA and the SRA is the demonstration that a reaction is significantly inhibited when excess heparin is added.…”

Section: Discussionsupporting

confidence: 66%

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

Padmanabhan

Jones²,

Bougie

et al. 2015

Blood

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Section: Discussionsupporting

confidence: 66%

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

Padmanabhan

Jones²,

Bougie

et al. 2015

Blood

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“…PF-4 binds to CS as well as to heparin-related GAGs (12,13,28,30,31), and is stored as a CS proteoglycan/PF-4 complex in ␣-granules of platelets (32,33). The affinity of PF-4 for different GAGs has been postulated to decrease in the order heparin Ͼ Ͼ HS Ͼ Ͼ DS Ͼ CSC Ͼ CSA (28).…”

Section: Pf-4 Binding To Neutrophil Glycosaminoglycansmentioning

confidence: 99%

Characterization of a Neutrophil Cell Surface Glycosaminoglycan That Mediates Binding of Platelet Factor 4

Petersen¹,

Brandt²,

Lindahl³

et al. 1999

Journal of Biological Chemistry

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“…A plasma factor with this property was first predicted inr 1948 by Conley (3) when he noticed that patients with thrombocytopenia had increased sensitivity to heparin. Partial purification of the specific, platelet-derived protein, referred to as platelet factor 4 (4), was reported by Deutsch et al (5), and, more recently, various investigators have published methods for isolation of the protein in an apparently homogeneous form (6)(7)(8)(9)(10)(11)(12)(13). Platelet factor 4 is a relatively small, heat-stable protein that is insoluble in solutions of low ionic strength, but that is soluble in high ionic strength solutions and in acidic buffers (12,13).…”

mentioning

confidence: 99%

“…Platelet factor 4 is a relatively small, heat-stable protein that is insoluble in solutions of low ionic strength, but that is soluble in high ionic strength solutions and in acidic buffers (12,13). Platelet factor 4 is released with and bound to a carrier proteoglycan molecule from which it is displaced by heparin (8,10).…”

mentioning

confidence: 99%

Amino acid sequence of human platelet factor 4.

Deuel¹,

Keim²,

Farmer³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

277

121

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Human platelet factor 4, a protein that binds heparin, has been purified to apparent homogeneity and the complete amino acid sequence of the protein has been determined. The 70-residue polypeptide chain contains no methionine, tryptophan, or phenylalanine, and contains only a single tyrosyl residue. The sequence analysis demonstrates a highly negatively charged amino-terminal region. The carboxyl-terminal region of the polypeptide is unusual in that it contains a repetitive clustering of positively charged and hydrophobic pairs of amino acids; preliminary evidence suggests that this domain may play a role in the binding of heparin.Heparin is a potent anticoagulant that is used extensively in clinical medicine for the treatment of thrombotic disease (1). Platelets release-a small protein that neutralizes the anticoagulant effect of heparin (2). A plasma factor with this property was first predicted inr 1948 by Conley (3) when he noticed that patients with thrombocytopenia had increased sensitivity to heparin. Partial purification of the specific, platelet-derived protein, referred to as platelet factor 4 (4), was reported by Deutsch et al. (5), and, more recently, various investigators have published methods for isolation of the protein in an apparently homogeneous form (6-13). Platelet factor 4 is a relatively small, heat-stable protein that is insoluble in solutions of low ionic strength, but that is soluble in high ionic strength solutions and in acidic buffers (12, 13). Platelet factor 4 is released with and bound to a carrier proteoglycan molecule from which it is displaced by heparin (8, 10).Because of a possible relationship of platelet factor 4 to arterial and venous thrombosis (14)(15)(16)(17)(18)(19)(20) tained by precipitation between ammonium sulfate concentrations of 50 and 100%, by affinity chromatography on columns of heparin-E-aminocaproic acid-Sepharose prepared as described by Schmer (21), and by gel filtration through Sephadex G-100 in 1 M NaCl. These methods and the modified thrombin time used in the assay of platelet factor 4 were adapted from those reported by Levine and Wohl (12). Purified platelet factor 4 binds 27 units of heparin per mg of protein.The purified protein appears as a single band after polyacrylamide gel electrophoresis (15% acrylamide) in the presence of sodium dodecyl sulfate and is estimated to be at least 95% pure both by this criterion and by automated Edman degradation of the intact S-carboxamidomethylated protein. The purity of the preparation was also established by immunological techniques. The IgG fraction of antisera obtained from rabbits immunized with platelet factor 4 was isolated by ammonium sulfate precipitation and DEAE-cellulose chromatography (22). The purified IgG gave a single precipitin line against purified platelet factor 4 in immunodiffusion experiments, suggesting that the purified protein behaves as a single major antigenic species.

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Characterization of a chondroitin 4-sulfate proteoglycan carrier for heparin neutralizing activity (platelet factor 4) released from human blood platelets☆

Cited by 176 publications

References 21 publications

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

Characterization of a Neutrophil Cell Surface Glycosaminoglycan That Mediates Binding of Platelet Factor 4

Amino acid sequence of human platelet factor 4.

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