MITOGENIC ACTIVITY OF BLOOD COMPONENTS .1. THROMBIN AND PROTHROMBIN
MITOGENIC ACTIVITY OF BLOOD COMPONENTS .1. THROMBIN AND PROTHROMBIN
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DOI：
10.1073/pnas.72.1.131
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发表时间：
1975-01-01
影响因子：
11.1
通讯作者：
BUCHANAN, JM
中科院分区：
文献类型：
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作者：
CHEN, LB;BUCHANAN, JM
当在不存在血清的情况下将凝血酶（EC 3.4.21.5）加入到静止的汇合的鸡胚成纤维细胞的培养基中时，凝血酶能够在12小时后刺激DNA合成，并在4天的时间内引起细胞数量的显著增加。与凝血酶相比，凝血酶原表现出低促有丝分裂活性。然而，在存在纯化的因子Xa（EC 3.4.21.6）和因子V的情况下，凝血酶原通过由成纤维细胞提供的“促凝血酶原激酶活性”转化为凝血酶。因此，凝血酶原，无论是纯化的还是作为血浆或血清的成分，都可以被认为是组织培养中促有丝分裂活性的储存库，除非培养基中存在的抗凝血酶的量足以中和所形成的凝血酶。通过使用蛋白酶的特异性抑制剂，并通过在BaSO 4上吸附分离凝血酶原，我们估计凝血酶原的潜在促有丝分裂活性约为用促凝血酶原激酶处理无纤维蛋白原血浆可获得的总活性的30-50%。除了促有丝分裂活性外，凝血酶还可以刺激细胞的迁移。凝血酶的这些实验说明，血液中的蛋白酶可以作为有效的有丝分裂原，并表明它们可能在伤口愈合过程中发挥作用。
When added to a culture medium of resting confluent chick embryo fibroblasts in the absence of serum, thrombin (EC 3.4.21.5) is able to stimulate DNA synthesis 12 hr later and to cause a substantial increase in cell number over a period of 4 days. As compared to thrombin, prothrombin exhibits low mitogenic activity. However, in the presence of purified Factor Xa (EC 3.4.21.6) and Factor V, prothrombin is converted to thrombin by "thromboplastin activity" supplied by the fibroblasts. Prothrombin, either purified or as a constituent of plasma or serum, may thus be considered to be a reservoir of mitogenic activity in tissue culture unless antithrombin is present in the culture medium in amounts sufficient to neutralize the thrombin formed. By use of a specific inhibitor of proteases, and by separation of prothrombin by absorption on BaSO4, we estimate that the potential mitogenic activity of prothrombin is approximately 30-50% of the total activity that can be obtained by treatment of fibrinogen-free plasma with thromboplastin. In addition to its mitogenic activity, thrombin can also stimulate the migration of cells. These experiments with thrombin illustrate that well-characterized proteases of blood can act as potent mitogens and suggest that they may play a role in the process of wound healing.