Intercellular calcium communication regulates platelet aggregation and thrombus growth.
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 alpha IIb beta 3 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.
Nesbitt
Warwick S
WS
Australian Centre for Blood Diseases, Department of Medicine, Monash University, Box Hill Hospital, Victoria 3128, Australia.
Giuliano
Simon
S
Kulkarni
Suhasini
S
Dopheide
Sacha M
SM
Harper
Ian S
IS
Jackson
Shaun P
SP
D000244:Adenosine Diphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology*; D014841:von Willebrand Factor / Q000502:physiology
D002614:Chelating Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018048:Receptors, Purinergic P2; D014841:von Willebrand Factor; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D002118:Calcium