PMID- 11488939 OWN - NLM STAT- MEDLINE DCOM- 20010823 LR - 20190910 IS - 0902-4441 (Print) IS - 0902-4441 (Linking) VI - 66 IP - 6 DP - 2001 Jun TI - Modulators of intraplatelet calcium concentration affect the binding of thrombospondin to blood platelets in healthy donors and patients with type 2 diabetes mellitus. PG - 396-403 AB - Thrombospondin (TSP), which is secreted from alpha-granules of activated platelets, binds to its surface receptor (CD36) in the presence of Ca2+. OBJECTIVES: We monitored how the modulation of intraplatelet Ca2+ 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 Ca2+ 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 microM 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 Ca2+ 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 Ca2+. Diabetic platelets seem more vulnerable to the releasers of cytosolic [Ca2+] and more resistant to the blockers of cytosolic [Ca2+] mobilisation. FAU - Wieclawska, B AU - Wieclawska B AD - Laboratory of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Lodz, Poland. FAU - Rozalski, M AU - Rozalski M FAU - Trojanowski, Z AU - Trojanowski Z FAU - Watala, C AU - Watala C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Haematol JT - European journal of haematology JID - 8703985 RN - 0 (CD36 Antigens) RN - 0 (P-Selectin) RN - 0 (Thrombospondins) RN - SY7Q814VUP (Calcium) SB - IM MH - Adult MH - Aged MH - Blood Platelets/drug effects/*metabolism MH - CD36 Antigens/drug effects/metabolism MH - Calcium/*metabolism MH - Diabetes Mellitus, Type 2/*blood MH - Female MH - Humans MH - Male MH - Matched-Pair Analysis MH - Middle Aged MH - P-Selectin/metabolism MH - Platelet Activation/drug effects MH - Protein Binding MH - Thrombospondins/drug effects/*metabolism EDAT- 2001/08/08 10:00 MHDA- 2001/08/24 10:01 CRDT- 2001/08/08 10:00 PHST- 2001/08/08 10:00 [pubmed] PHST- 2001/08/24 10:01 [medline] PHST- 2001/08/08 10:00 [entrez] AID - ejh466 [pii] AID - 10.1034/j.1600-0609.2001.066006396.x [doi] PST - ppublish SO - Eur J Haematol. 2001 Jun;66(6):396-403. doi: 10.1034/j.1600-0609.2001.066006396.x.