Influence of heat on platelet biochemistry, structure, and function.
The present investigation has evaluated the influence of temperatures ranging from 37 degrees C to 45 degrees C for intervals of 30, 60, and 90 minutes on the biochemistry, morphology, and function of human platelets. Exposure to temperatures up to 43 degrees C for an hour did not significantly alter platelet morphology or physiologic response to aggregating agents. Samples of platelets heated at 43 degrees for 60 minutes lost their ability to aggregate in response to arachidonate, but sensitivity was restored by pretreatment with epinephrine. Platelets heated to 45 degrees C for 90 minutes were converted from discs to spheres and failed to aggregate in response to all agonists, whether or not they were pretreated with epinephrine. The platelets heated at 45 degrees C for 90 minutes could adhere to formvar or denuded subendothelium but were unable to extend pseudopods or to spread. They maintained normal levels of adenine nucleotides and serotonin but failed to secrete these products on stimulation. Studies with fibrinogen coupled to gold (Fgn/Au) revealed only a few particles bound to glycoprotein IIb-IIIa (GPIIb-IIIa) on platelets heated at 43 degrees C for 90 minutes. Ligands that did bind to GPIIb-IIIa were transported to the open canalicular system. Biochemical studies demonstrated normal synthesis of thromboxane B2 and calcium flux by platelets heated at 45 degrees C for 90 minutes. Polyacrylamide gels of platelets heated at 45 degrees C for 90 minutes showed an increase in talin incorporation into heated platelet cytoskeletons but no increase in filamentous actin. The findings indicate that impaired function of heated platelets is due to the influence of heat on cytoskeletal proteins important for pseudopod extension, shape change, expression of GPIIb-IIIa, or other surface membrane receptors and secretion, but that impaired function is not due to inhibition of biochemical systems involved in activation events.
Rao
G H
GH
Department of Pediatrics, University of Minnesota Health Sciences Center, Minneapolis.
Smith
C M
CM
Escolar
G
G
White
J G
JG
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000818:Animals; D001011:Aorta / Q000502:physiology; D016718:Arachidonic Acid / Q000097:blood / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D003599:Cytoskeleton / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000097:blood; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
D001798:Blood Proteins; D011450:Prostaglandin Endoperoxides, Synthetic; D016718:Arachidonic Acid; D012701:Serotonin; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D013917:Thrombin; D002118:Calcium; D004837:Epinephrine