Yui N, Suzuki K, Okano T, Sakurai Y, Nakano M, Ishikawa C, Fujimoto K, Kawaguchi H
School of Materials Science, Japan Advanced Institute of Science and Technology, Ishikawa.
J Biomater Sci Polym Ed. 1995;7(3):253-64. doi: 10.1163/156856295x00292.
Changes in cytoplasmic free calcium levels and membrane fluidity of platelets in contact with poly(acrylamide-co-methacrylic acid) (PAAmMAc) particles were examined to analyze the mechanistic aspect of regulating platelet function. Our previous studies demonstrated interesting features of PAAmMAc particles during interaction with platelets: (1) PAAmMAc particles induce no calcium increase but enhance membrane fluidity of platelets: (2) thrombin induces no calcium increase in platelets when the platelets were mixed previously with PAAmMAc particles; and (3) PAAmMAc particles induce a calcium increase in platelets when they were treated previously with sodium azide (NaN3). These results suggest the possibility that PAAmMAc surfaces may regulate the calcium level by influencing platelet metabolism. In this study, non-cross-linked PAAmMAc solution with the same chemical composition as the particles showed a suppressive effect on thrombin-induced calcium increase, but, no influence on membrane fluidity. This result indicates that aggregated macromolecular surface assemblies of PAAmMAc may dominate the increase in membrane fluidity of platelets although the calcium change is induced by discrete molecular level interaction between the PAAmMAc and platelet membranes. It was also revealed that the suppression of thrombin-induced calcium increase and the membrane fluidity increase in platelets by PAAmMAc particles were reduced by albumin-treatment of the particles. This result suggests that such phenomena may be due to a decrease in any physicochemical interaction of PAAmMAc surfaces with albumin, rather than platelet metabolic change. PAAmMAc particle surfaces with higher carboxyl groups exhibited a more suppressive effect on thrombin-induced calcium increase, whereas those with lower carboxyl groups derived a higher calcium increase when the platelets were treated previously with NaN3. These results suggest the importance of electrostatic and any other physicochemical interaction of PAAmMAc chains on regulating cytoplasmic calcium levels.
为了分析调节血小板功能的机制,研究了与聚(丙烯酰胺 - 共 - 甲基丙烯酸)(PAAmMAc)颗粒接触的血小板细胞质游离钙水平和膜流动性的变化。我们之前的研究揭示了PAAmMAc颗粒与血小板相互作用过程中的有趣特征:(1)PAAmMAc颗粒不会引起钙增加,但会增强血小板的膜流动性;(2)当血小板预先与PAAmMAc颗粒混合时,凝血酶不会引起血小板钙增加;(3)当PAAmMAc颗粒预先用叠氮化钠(NaN3)处理时,会引起血小板钙增加。这些结果表明PAAmMAc表面可能通过影响血小板代谢来调节钙水平。在本研究中,具有与颗粒相同化学成分的非交联PAAmMAc溶液对凝血酶诱导的钙增加有抑制作用,但对膜流动性没有影响。这一结果表明,尽管钙变化是由PAAmMAc与血小板膜之间离散的分子水平相互作用引起的,但PAAmMAc的聚集大分子表面组装可能主导了血小板膜流动性的增加。还发现,通过白蛋白处理颗粒,PAAmMAc颗粒对凝血酶诱导的钙增加和血小板膜流动性增加的抑制作用减弱。这一结果表明,此类现象可能是由于PAAmMAc表面与白蛋白的任何物理化学相互作用减少,而非血小板代谢变化所致。具有较高羧基的PAAmMAc颗粒表面对凝血酶诱导的钙增加表现出更强的抑制作用,而具有较低羧基的颗粒在血小板预先用NaN3处理时会引起更高的钙增加。这些结果表明PAAmMAc链的静电和任何其他物理化学相互作用在调节细胞质钙水平方面的重要性。