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Modulators of intraplatelet calcium concentration affect the binding of thrombospondin to blood platelets in healthy donors and patients with type 2 diabetes mellitus
Author(s) -
Wieclawska Boguslawa,
Rozalski Marcin,
Trojanowski Zygmunt,
Watala Cezary
Publication year - 2001
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1034/j.1600-0609.2001.066006396.x
Subject(s) - egta , cd36 , platelet , medicine , endocrinology , platelet activation , thrombospondin , calcium , chemistry , diabetes mellitus , receptor , metalloproteinase , matrix metalloproteinase
Thrombospondin (TSP), which is secreted from α‐granules of activated platelets, binds to its surface receptor (CD36) in the presence of Ca 2+ . Objectives : We monitored how the modulation of intraplatelet Ca 2+ affects TSP binding to CD36 on platelets from healthy donors and patients with type 2 diabetes mellitus. We also aimed to verify whether the impaired Ca 2+ mobilisation in diabetes influences TSP binding upon the pharmacological modulation of calcium transport. Methods : Whole blood cytometry was used to monitor TSP release/binding and CD36 presentation in platelets from 28 type 2 patients and 33 healthy donors. Results : No significant changes in TSP and CD36 levels were revealed between the groups in circulating platelets and TRAP‐, collagen‐ or thrombin‐activated platelets. In healthy donors, 1 µM thapsigargin (TG) elevated the TRAP‐activated TSP binding (by up to 50%, p <0.001), 5 mM EGTA reversed the effect (by up to 85%, p <0.001), and overcame the effect of TG when used together. Less profoundly expressed effects occurred in the NIDDM group. In both groups TG increased the presentation of CD36 in TRAP‐stimulated platelets ( p <0.05), whereas EGTA lowered the TRAP‐stimulated increase in CD36 ( p <0.001). The inhibition of CD36 by EGTA was stronger in healthy volunteers (41% vs. 32%, respectively, p <0.05), whereas the activation by TG was higher in the NIDDM group (11% vs. 27%, p <0.05). When acting together the suppressive effects of EGTA on TG‐dependent Ca 2+ mobilisation were much attenuated in diabetic subjects ( p <0.05). Conclusion : Both the release of TSP and CD36 presentation are under the influence of agents modulating intracellular Ca 2+ . Diabetic platelets seem more vulnerable to the releasers of cytosolic [Ca 2+ ] and more resistant to the blockers of cytosolic [Ca 2+ ] mobilisation.