EVIDENCE FOR A STRUCTURAL REQUIREMENT FOR AGGREGATION OF PLATELETS BY COLLAGEN
EVIDENCE FOR A STRUCTURAL REQUIREMENT FOR AGGREGATION OF PLATELETS BY COLLAGEN
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DOI：
10.1172/jci107628
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发表时间：
1974-01-01
影响因子：
15.9
通讯作者：
DEYKIN, D
中科院分区：
文献类型：
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作者：
JAFFE, R;DEYKIN, D
本研究探讨可溶性胶原蛋白是否可以引发血小板聚集或是否需要更高的聚合度。制备了四种状态的纯化大鼠皮肤胶原蛋白。将含有2 μM氯化钙的可溶性单体胶原保持在4 ℃下直至使用。一种先前未表征的胶原形式，可溶性微纤维胶原，是由含有氯化钙的单体胶原通过在23°C下使其溶解而制备的。微纤维胶原的粘度和电子显微镜表征表明聚合成有序的天然细丝。通过在不存在钙的情况下使其在37°C下煅烧，从单体胶原制备颗粒状天然大原纤维胶原。通过无钙单体胶原的盐沉淀制备纤维随机结合的颗粒胶原。微原纤维和天然大原纤维胶原蛋白引发血小板聚集，滞后期约为60 s。单体胶原以约180秒的滞后期引发聚集。由单体胶原引发的血小板聚集的滞后期的持续时间与剂量无关。盐沉淀的颗粒胶原蛋白不引发血小板聚集。延长从单体胶原到纤维状胶原的转变的试剂（尿素、精氨酸）延迟或防止单体胶原引起的血小板聚集。硼氢化钠稳定胶原分子内和分子间的交联，不影响血小板聚集。青霉胺，它取代了分子间交联和结合的胶原分子内交联，并没有阻止血小板聚集。这些数据表明，存在一个结构要求，以启动自我永存血小板聚集;原胶原单位不满足这一要求;可溶性胶原蛋白制剂，微纤维胶原蛋白，含有最小的结构单元;胶原蛋白内的交联在血小板聚集中不起关键作用。图片
This study investigates whether soluble collagen can initiate platelet aggregation or whether a higher degree of polymerization is required. Purified rat skin collagen was prepared in four states. Soluble monomeric collagen, containing 2 μM calcium chloride, was maintained at 4°C until use. A previously uncharacterized form of collagen, soluble microfibrillar collagen, was prepared from monomeric collagen containing calcium chloride by allowing it to polymerize at 23°C. Viscometric and electron microscopic characterization of microfibrillar collagen indicated polymerization to ordered native filaments. Particulate native macrofibrillar collagen was prepared from monomeric collagen by allowing it to polymerize at 37°C in the absence of calcium. Particulate collagen, in which the fibers were randomly associated, was prepared by salt precipitation of calcium-free monomeric collagen. Microfibrillar and native macrofibrillar collagen initiated platelet aggregation, with a lag phase of approximately 60 s. Monomeric collagen initiated aggregation with a lag phase of approximately 180 s. The duration of the lag phase for platelet aggregation initiated by monomeric collagen was independent of the dose. Salt-precipitated particulate collagen did not initiate platelet aggregation. Agents which prolong the transition from monomeric collagen to fibrillar collagen (urea, arginine) retarded or prevented the aggregation of platelets by monomeric collagen. Sodium borohydride, which stabilizes the intraand intermolecular cross-links of collagen did not affect platelet aggregation. Penicillamine, which displaces the intermolecular cross-links and binds the intramolecular cross-links of collagen, did not prevent platelet aggregation. The data suggest that an architectural requirement exists for the initiation of self-perpetuating platelet aggregation; that tropocollagen units do not fulfill this requirement; that a soluble collagen preparation, microfibrillar collagen, contains the minimal structural unit; and that cross-linkages within collagen do not play a critical role in platelet aggregation.Images