Chesney C M, Pifer D D, Crofford L J, Huch K M
Am J Pathol. 1983 Aug;112(2):200-6.
Chemical modification of collagen is a tool for exploring the platelet-collagen interaction. Since collagen must polymerize prior to the initiation of platelet aggregation and secretion, modification must be shown to affect platelet-collagen interaction and not collagen-collagen interaction. To address this point, the authors carried out the following chemical modifications on soluble monomeric collagen and preformed fibrillar collagen in parallel: 1) N-and O-acetylation, 2) esterification of the carboxyl groups, 3) succinylation of the free amino groups, 4) esterification of succinylated collagen. Intrinsic viscosity studies of the modified soluble collagens were consistent with normal triple helix conformation. Electron microscopy revealed all modified fibrillar collagen to maintain a fibrillar structure. Platelet aggregation and secretion of 14C-serotonin and platelet factor 4 by soluble and fibrillar collagen, respectively, were studied in human platelet-rich plasma. Neutralization of polar groups by 1) totally abolished aggregation and secretion by both collagens, while blocking acidic groups 2) resulted in enhanced aggregation and secretion by both soluble and fibrillar collagen. Blockage of amino groups by 3) abolished aggregation and secretion by both collagens. Esterified succinylated collagen 4) caused aggregation and secretion at relatively high collagen concentrations. These data support the theory that positive groups of collagen are important in platelet-collagen interaction.
胶原蛋白的化学修饰是探索血小板与胶原蛋白相互作用的一种手段。由于胶原蛋白在血小板聚集和分泌开始之前必须聚合，因此必须证明修饰会影响血小板与胶原蛋白的相互作用，而不是胶原蛋白与胶原蛋白的相互作用。为了阐明这一点，作者对可溶性单体胶原蛋白和预先形成的纤维状胶原蛋白同时进行了以下化学修饰：1）N-和O-乙酰化，2）羧基酯化，3）游离氨基琥珀酰化，4）琥珀酰化胶原蛋白的酯化。对修饰后的可溶性胶原蛋白进行的特性粘度研究与正常的三螺旋构象一致。电子显微镜显示所有修饰后的纤维状胶原蛋白均保持纤维状结构。在富含人血小板的血浆中，分别研究了可溶性和纤维状胶原蛋白诱导的血小板聚集、14C-血清素分泌以及血小板因子4的分泌情况。1）通过中和极性基团完全消除了两种胶原蛋白诱导的聚集和分泌，而2）通过阻断酸性基团导致可溶性和纤维状胶原蛋白诱导的聚集和分泌增强。3）通过阻断氨基消除了两种胶原蛋白诱导的聚集和分泌。4）酯化的琥珀酰化胶原蛋白在相对较高的胶原蛋白浓度下会引起聚集和分泌。这些数据支持了胶原蛋白的正电荷基团在血小板与胶原蛋白相互作用中很重要这一理论。
