title: Marked temperature dependence of the platelet calcium signal induced by human von Willebrand factor.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Kermode
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.forename: E P
authors.initials: EP
authors.lastname: Milner
mesh_terms: 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*
chemical_list: D014841:von Willebrand Factor; D002118:Calcium