SIGNIFICANCE OF TESTING PLATELET FUNCTIONS IN-VITRO
SIGNIFICANCE OF TESTING PLATELET FUNCTIONS IN-VITRO
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DOI：
10.1111/j.1365-2362.1994.tb02418.x
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发表时间：
1994-02-01
影响因子：
5.5
通讯作者：
HOLMSEN, H
中科院分区：
文献类型：
--
作者：
HOLMSEN, H
血小板通过离散的受体对许多生理激动剂和外来表面作出反应，并通过一系列可测量的反应：形状变化、聚集、分泌和花生四烯酸释放。有三种分泌反应：来自(1)致密颗粒、(2)α颗粒和(3)溶酶体的物质的胞吐。游离的花生四烯酸被磷脂酶A(2)从磷脂中释放出来，通过氧合作用迅速转化为前列腺素和血栓烷，与分泌的ADP和密切的细胞接触一起，将通过‘正反馈’(自分泌刺激)引起进一步的血小板激活。有些激动剂被归类为“弱”激动剂(ADP、加压素、血小板激活因子[PAF]、5-羟色胺)，因为它们依赖自分泌刺激来促进整个反应序列，而另一些则是“强”激动剂(凝血酶、胶原蛋白)，直接激活所有反应，而不需要自分泌刺激。肾上腺素，长期以来被认为本身是一种血小板激动剂，很可能是通过放大其他适当的激动剂带来的激活而起作用的。激动剂之间的这种协同作用对于血小板激活来说是非常典型的，而且很可能发生在体内。形态改变、聚集和分泌(S)可以在体外用流式细胞仪或电子显微镜在可能反映体内情况的条件下进行检测。然而，体外对弱激动剂的聚集反应依赖于细胞外[Ca~(2+)]，当柠檬酸盐用作抗凝剂(或在洗涤的血小板悬浮液中)时，双相聚集在低[Ca~(2+)]处，而不是在肝素化血液中富含血小板的血浆中的生理[Ca~(2+)]。
Platelets respond through discrete receptors to a number of physiological agonists and foreign surfaces with a sequence of measurable responses: shape change, aggregation, secretion and arachidonate liberation. Three secretory responses are distinguished: exocytosis of substances from (1) dense granules, (2) alpha-granules and (3) lysosomes. Free arachidonate, liberated from phospholipids by phospholipase A(2), is rapidly converted (by oxygenation) to prostaglandins and thromboxanes which, together with secreted ADP and close cell contact, will cause further platelet activation through 'positive feedback' (autocrine stimulation). Some agonists are classified as 'weak' (ADP, vasopressin, platelet-activating factor [PAF], serotonin) because they depend on autocrine stimulation to promote the full sequence of responses, while others are 'strong' agonists (thrombin, collagen) and activate all responses directly without autocrine stimulation. Adrenaline, long thought to be a platelet agonist per se, most probably acts by amplifying the activation brought about by other, proper, agonists. Such synergistic interaction among agonists is very typical for platelet activation and most likely takes place in vivo. Shape change, aggregation and secretion(s) may be tested by flow cytometry or electron microscopy in vitro under conditions that probably reflect the in vivo situation. However, the aggregation response to weak agonists in vitro is dependent on the extracellular [Ca2+], with biphasic aggregation at the low [Ca2+] present when citrate is used as anticoagulant (or in suspension of washed platelets) but not at the physiological [Ca2+] present in platelet-rich plasma from heparinized blood.