The Effect of Temperature Variation In Vitro on Platelet-Leukocyte Interactions and Individual Prothrombotic Potential
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BACKGROUND: Temperature variation within human atheromatous plaques, a finding which supports inflammatory cell-mediated thermogenesis, predicts clinical events among patients with coronary artery disease. PURPOSE: Our study was designed to investigate the effect of ambient temperature in vitro on platelet-leukocyte interactions, monocyte tissue factor expression and platelet-dependent thrombin generation. METHODS/RESULTS: Whole blood samples obtained from healthy volunteers were incubated at 37 degrees, 38 degrees and 39 degrees C for three hours. Platelet-leukocyte aggregates, determined by flow cytometry before and after stimulation with lipopolysaccharide (10 ng/ml), increased from 15.0 +/- 2.3% at 37 degrees C to 19.4% at 38 degrees C (22.6% increase; p < 0.01), decreasing to 12.2 +/- 0.9% at 39 degrees C. The responses for individual subpopulations of platelet-lymphocyte, platelet-neutrophil and platelet-monocyte heterotypic aggregates were similar. Monocyte tissue factor expression, quantitated by flow cytometry with CD14 and FITC-labeled anti-human tissue factor antibody stains, increased from 45.2 +/- 3.8% (37 degrees C) to 62.0 +/- 4.3 (38 degrees C), representing a 27.1% rise (p < 0.005). Changes in temperature did not influence the initiation or propagation phases of platelet-dependent thrombin generation. CONCLUSION: A modest increase in ambient temperature increases platelet-leukocyte and monocyte tissue factor expression, providing an additional mechanistic link between atherosclerosis, inflammation and thrombosis. Whether therapies designed to lower vessel wall temperature will provide an antithrombotic effect requires further evaluation.