Marked temperature dependence of the platelet calcium signal induced by human von Willebrand factor.
Interaction of von Willebrand factor (vWF) with the platelet is essential to hemostasis when vascular injury occurs. This interaction elevates the intracellular free calcium concentration ([Ca2+]i) and promotes platelet activation. The present study investigated the temperature dependence of vWF-induced [Ca2+]i signaling in human platelets. The influence of temperature can provide invaluable insight into the underlying mechanism. Platelet [Ca2+]i was monitored with Fura-PE3. Ristocetin-mediated binding of vWF induced a transient platelet [Ca2+]i increase at 37 degrees C, but no response at lower temperatures (20 degrees C to 25 degrees C). This temperature dependence could not be attributed to a reduction in vWF binding, as ristocetin-mediated platelet aggregation and agglutination were essentially unaffected by temperature. Most other platelet agonists (U-46619, alpha-thrombin, and adenosine 5'-diphosphate [ADP]) induced a [Ca2+]i signal whose amplitude did not diminish at lower temperatures. The [Ca2+]i signal in response to arachidonic acid, however, showed similar temperature dependence to that seen with vWF. Assessment of thromboxane A2 production showed a strong temperature dependence for metabolism of arachidonic acid by the cyclo-oxygenase pathway. vWF induced thromboxane A2 production in the platelet. Aspirin treatment abolished the vWF-induced [Ca2+]i signal. These observations suggest that release of arachidonic acid and its conversion to thromboxane A2 play a central role in vWF-mediated [Ca2+]i signaling in the platelet at physiological temperatures.
Kermode
J C
JC
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Zheng
Q
Q
Milner
E P
EP
D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013696:Temperature; D014841:von Willebrand Factor / Q000494:pharmacology*
D014841:von Willebrand Factor; D002118:Calcium