The in vivo release of human platelet factor 4 by heparin

Dawes, J.; Pumphrey, C W; McLaren, K M; Prowse, Christopher V.; Pepper, Duncan S.

doi:10.1016/0049-3848(82)90279-1

Cited by 110 publications

(50 citation statements)

References 16 publications

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“…In clinical studies Ͼ20 years ago, it was observed that heparin increases the circulating levels of platelet factor 4 (PF4)/CXCL4 in both healthy volunteers and patients with coronary atherosclerosis. 22,23 Further investigations revealed that heparin displaced PF4 from cultured endothelial cells 24 but not whole blood, 22 similar to our findings that IP-10 was detected in the supernatant of heparin-treated HUVECs but not PBMCs. Moreover, PF4 and IP-10 share the same binding site on cell-surface GAG, and endothelial cells contain Ͼ1000-fold more binding sites for IP-10 than leukocytes.…”

Section: Discussionsupporting

confidence: 76%

Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells

et al. 2006

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Background-Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-␥ responses in endothelial cells. We investigated the effects of heparin on the IFN-␥-inducible chemokines IP-10/CXCL10, I-TAC/CXCL11, and Mig/CXCL9, which play important roles in the vascular recruitment of IFN-␥-producing Th1 cells through interactions with their cognate receptor, CXCR3. Methods and Results-Patients undergoing coronary artery bypass grafting were studied because coronary atherosclerosis is recognized as a Th1-type inflammatory disease and the subjects required systemic heparinization. Plasma levels of IP-10, I-TAC, and Mig increased immediately after heparin administration and diminished promptly after heparin antagonism with protamine. These effects were independent of detectable circulating IFN-␥ or the IFN-␥ inducer interleukin-12. We confirmed previous reports that heparin inhibits the IFN-␥-dependent production of CXCR3 chemokine ligands using atherosclerotic coronary arteries in organ culture. In addition to prolonged treatment decreasing chemokine secretion, heparin rapidly displaced membrane-associated IP-10 from cultured endothelial cells that did not express CXCR3 and reduced the IP-10 -dependent transendothelial migration of T helper cells under conditions of venular shear stress. Finally, heparin administration to immunodeficient mouse hosts decreased both the recruitment and accumulation of memory T cells within allogeneic human coronary arteries. Conclusions-Besides

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Section: Discussionsupporting

confidence: 76%

Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells

et al. 2006

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“…33 An advantage of the use of heparin-bonded catheters for investigative studies is that the need for systemic heparinization is eliminated. Systemic heparinization is routinely used during most cardiac catheterization and angiographic procedures to prevent catheter-induced thromboembolic complications.…”

Section: Discussionmentioning

confidence: 99%

Effect of heparin bonding on catheter-induced fibrin formation and platelet activation.

Nichols¹,

Owen²,

Grossman³

et al. 1984

Circulation

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Pathologic and experimental evidence indicates that platelet activation and fibrin formation contribute to the pathogenesis of angina pectoris, coronary vasospasm and myocardial infarction. Detection of localized intravascular platelet activation and fibrin formation in vivo by selective blood sampling requires catheters that do not induce coagulation ex vivo. We studied the effect of heparin bonding of catheter surfaces on activation of the coagulation system by cardiovascular catheters. Woven Dacron, polyvinylchloride, and polyurethane catheters were tested and compared with identical catheters with heparin-bonded surfaces in 47 patients undergoing percutaneous cardiac catheterization. Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), /3-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels. In blood samples collected through conventional catheters, FPA, PF4, BTG, and TXB2 levels were markedly elevated; blood sampling through heparin-bonded catheters had no significant effect on FPA, PF4, BTG, or TXB2 levels. Scanning electron microscopy disclosed extensive platelet aggregates and fibrin strands adherent to the surface of conventional catheters but not to heparin-bonded catheter surfaces. This study demonstrates that (1) collection of blood samples through cardiovascular catheters causes artifactual elevation of FPA, PF4, BTG, and TXB2 levels, and (2) heparin-bonded catheter surfaces effectively prevent catheter-induced platelet a-granule release and fibrin formation on catheter surfaces. Heparin-bonded catheters will facilitate investigation of the role of intravascular coagulation in coronary artery disease by eliminating catheter-induced fibrin formation and platelet activation. Circulation 70, No. 5, 843-850, 1984. RECENT clinical and experimental evidence suggests that platelet activation and fibrin formation in vivo may be fundamentally important in clinical complications of atherosclerotic coronary artery disease, including unstable angina,1 myocardial infarction,24 and sudden death.5 Investigation of platelet release and fibrin formation in vivo has been facilitated by the recent development of radioimmunoassays for specific proteins and prostanoids released by activated platelets6'7 and peptides released during fibrin formation.8Platelet factor 4 (PF4) and ,3-thromboglobulin (BTG) are platelet-specific proteins secreted from platelet agranules during the platelet-release reaction.9 10

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“…The saturability and the possibility to induce the displacement of labeled heparin by injecting large amounts of unlabeled heparin, observed in vivo in the present study, suggest the presence of binding sites for heparin on the endothelial surface. Specific binding sites for heparin on the sur face of cultured human endothelial cells de rived from the umbilical vein were shown by Glimelius et al [3], Moreover, also indirect evidence of the interaction between heparin and the endothelium was provided by Dawes et al [6], who demonstrated that heparin is able to cause the release of platelet factor 4 from the vascular endothelium.…”

Section: Discussionmentioning

confidence: 91%

Binding of Low-Molecular-Weight Heparin to Aortic Endothelium in Rabbits

Gensini

Fortini

Lombardi

et al. 1984

Pathophysiol Haemos Thromb

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The ability of a low-molecular-weight heparin to bind in vivσto the aortic endothelium in rabbits, compared with that of unfractionated extractive sodium heparin (UHEP), was investigated. For this purpose a low-molecular-weight heparin (LMWHEP) fraction (CY 216 A, 4,000–5,000 daltons) and an extractive UHEP (average 17,000 daltons) were labeled with ^99mTc and injected (0.2, 0.6, and 1.2 mg/kg) intravenously in groups of 6 rabbits. The binding to endothelium was then measured by counting the radioactivity of samples of abdominal aorta. Both heparins bound to endothelium with a fast, saturable, and reversible binding. No significant difference in the total bound radioactivity was found between the two heparins, suggesting that the investigated LMWHEP retains the ability to bind to the endothelium, contributing to its athrombogenic properties.

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The in vivo release of human platelet factor 4 by heparin

Cited by 110 publications

References 16 publications

Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells

Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells

Effect of heparin bonding on catheter-induced fibrin formation and platelet activation.

Binding of Low-Molecular-Weight Heparin to Aortic Endothelium in Rabbits

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