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© The Rockefeller University Press, 0021-9525/2003/3/1151 $5.00
The Journal of Cell Biology, Volume 160, Number 7, 1151-1161

Intercellular calcium communication regulates platelet aggregation and thrombus growth

Australian Centre for Blood Diseases, Department of Medicine, Monash University, Box Hill Hospital, Victoria 3128, Australia

Address correspondence to Shaun P. Jackson, Australian Centre for Blood Diseases, Department of Medicine, Monash University, Box Hill Hospital, Arnold St., Box Hill, Melbourne, Victoria 3128, Australia. Tel.: 03-9895-0350. Fax: 03-9895-0332. E-mail: shaun.jackson{at}med.monash.edu.au

The ability of platelets to form stable adhesion contacts with other activated platelets (platelet cohesion or aggregation) at sites of vascular injury is essential for hemostasis and thrombosis. In this study, we have examined the mechanisms regulating cytosolic calcium flux during the development of platelet–platelet adhesion contacts under the influence of flow. An examination of platelet calcium flux during platelet aggregate formation in vitro demonstrated a key role for intercellular calcium communication (ICC) in regulating the recruitment of translocating platelets into developing aggregates. We demonstrate that ICC is primarily mediated by a signaling mechanism operating between integrin _IIbß₃ and the recently cloned ADP purinergic receptor P2Y₁₂. Furthermore, we demonstrate that the efficiency by which calcium signals are propagated within platelet aggregates plays an important role in dictating the rate and extent of thrombus growth.

Key Words: blood platelets; cell adhesion; thrombosis; calcium signaling; integrin_IIbß3

The online version of this article includes supplemental material.

^* Abbreviations used in this paper: GP, glycoprotein; ICC, intercellular calcium communication; TXA₂, thromboxane A₂; vWf, von Willebrand factor.

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