Blood, Vol. 94 No. 1 (July 1), 1999:
pp. 199-207
Marked Temperature Dependence of the Platelet Calcium Signal
Induced by Human von Willebrand Factor
John C. Kermode,
Qi Zheng, and
Elizabeth P. Milner
From the Department of Pharmacology and Toxicology, University of
Mississippi Medical Center, Jackson, MS.
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°C, but no
response at lower temperatures (20°C to 25°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, 
-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.
