Eichinger Colin D, Hlady Vladimir
Department of Bioengineering, University of Utah, 20 S. 2030 E., Rm. 108A, Salt Lake City, Utah 84112.
Biointerphases. 2017 Apr 28;12(2):02C406. doi: 10.1116/1.4982596.
As platelets encounter damaged vessels or biomaterials, they interact with a complex milieu of surface-bound agonists, from exposed subendothelium to adsorbed plasma proteins. It has been shown that an upstream, surface-immobilized agonist is capable of priming platelets for enhanced adhesion downstream. In this study, binary agonists were integrated into the upstream position of flow cells and the platelet priming response was measured by downstream adhesion in flowing whole blood. A nonadditive response was observed in which platelets transiently exposed to two agonists exhibited greater activation and downstream adhesion than that from the sum of either agonist alone. Antibody blocking of one of the two upstream agonists eliminated nonadditive activation and downstream adhesion. Crosstalk between platelet activation pathways likely led to a synergistic effect which created an enhanced activation response in the platelet population. The existence of synergy between platelet priming pathways is a concept that has broad implications for the field of biomaterials hemocompatibility and platelet activity testing.
当血小板遇到受损血管或生物材料时，它们会与表面结合的激动剂的复杂环境相互作用，从暴露的内皮下层到吸附的血浆蛋白。研究表明，上游表面固定的激动剂能够使血小板致敏，从而增强下游的黏附。在本研究中，将二元激动剂整合到流动腔室的上游位置，并通过流动全血中的下游黏附来测量血小板致敏反应。观察到一种非加性反应，即短暂暴露于两种激动剂的血小板比单独使用任何一种激动剂时表现出更大的活化和下游黏附。对两种上游激动剂之一进行抗体阻断可消除非加性活化和下游黏附。血小板活化途径之间的串扰可能导致协同效应，从而在血小板群体中产生增强的活化反应。血小板致敏途径之间协同作用的存在这一概念对生物材料血液相容性和血小板活性测试领域具有广泛的意义。
