Interaction of platelet factor 4 with human platelets

Anna M. Capitanio, Stefan Niewiarowski, Boguslaw Rucinski, George P. Tuszynski, Czeslaw S. Cierniewski, Diane Hershock, Elizabeth Kornecki

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Abstract

Human washed resting platelets bound 125I-labeled platelet factor 4 in a reaction which was saturable and approached equilibrium within 15-30 min. Scatchard plot analysis of the binding isotherms suggested a single class of specific binding sites. Excess of unlabeled protein and low- and high-affinity heparin competed for platelet factor 4 binding sites on the platelet surface and caused a partial displacement of this molecule. Anti-platelet factor 4 Fab fragments caused inhibition of binding of 125I-platelet factor 4 to platelets. Most of the labeled platelet factor 4 which was bound to intact platelets was recovered in the Triton X-100-insoluble cytoskeletal fraction prepared from the same platelets after their stimulation by thrombin. The association with the cytoskeleton was inhibited by anti-platelet factor 4 Fab fragments and by low-affinity heparin. Anti-platelet factor 4 125I-labeled Fab fragments bound to resting platelets, and this binding was greatly increased following platelet stimulation with thrombin. This suggested that endogenously secreted platelet factor 4 also binds to the platelet surface. No significant binding to platelets of 125I-labeled β-thromboglobulin and 125I-labeled anti-β-thromboglobulin Fab fragments was observed. Fab fragments of monospecific anti-human platelet factor 4 antibody raised in rabbits inhibited platelet aggregation and secretion induced by low concentrations of thrombin. Fab fragments of anti-β-thromboglobulin antibody had no inhibitory effect. We suggest that the binding of α-granule-derived platelet factor 4 to the specific sites on the surface of platelets may modulate platelet gregation and secretion induced by low levels of platelet agonists.

Original languageEnglish (US)
Pages (from-to)161-173
Number of pages13
JournalBBA - General Subjects
Volume839
Issue number2
DOIs
StatePublished - Apr 17 1985

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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    Capitanio, A. M., Niewiarowski, S., Rucinski, B., Tuszynski, G. P., Cierniewski, C. S., Hershock, D., & Kornecki, E. (1985). Interaction of platelet factor 4 with human platelets. BBA - General Subjects, 839(2), 161-173. https://doi.org/10.1016/0304-4165(85)90033-9