Carson S D, De Jonge C J
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-6495, USA.
J Androl. 1998 May-Jun;19(3):289-94.
Tissue factor (TF) is an essential cofactor for factor VII (fVII) in initiating blood coagulation. Recently, TF was shown to be present in human semen and to be associated with prostasomes that originate from prostatic secretions. In the blood coagulation cascade, the complex of TF and activated factor VII (fVIIa) can activate both factor X and factor IX, by limited proteolysis. In the present study, we investigated the ability of semen to activate factor X. We also determined that factor X was activated predominantly by TF-fVIIa and that most of the TF was present in the seminal plasma, consistent with prostasome localization. No endogenous factor X was detected in semen, but activation of added factor X occurred in the absence of added fVIIa. Subsequent experiments showed that seminal plasma contains endogenous fVII-like activity, but the addition of more fVIIa increased factor X activation. Thus, while seminal plasma contains significant amounts of TF, its potential to activate factor X is limited by fVII availability and by the absence of endogenous factor X. Evaluation of semen specimens from infertility patients revealed a 16-fold variation in TF-fVII activity. No relationship between TF and number of days of abstinence, specimen pH, sperm count, or sperm motility was evident. Additional factor X-activating potential, independent of further TF activity, was generated in seminal plasma after treatment of semen with calcium and ionophore A23187. Production of this additional activity was blocked by the addition of anti-TF antibody during the activation. Since there is no factor X endogenous to semen, the additional activity stimulated by A23187 appears to be due to an endogenous, non-factor X substrate for TF-fVII in semen. This endogenous substrate may be either factor IX or a novel new substrate for TF-fVIIa. Future experiments will test these hypotheses.
组织因子(TF)是启动血液凝固过程中因子VII(fVII)的必需辅因子。最近研究表明,TF存在于人类精液中,并与源自前列腺分泌物的前列腺小体相关。在血液凝固级联反应中,TF与活化的因子VII(fVIIa)形成的复合物可通过有限的蛋白水解作用激活因子X和因子IX。在本研究中,我们调查了精液激活因子X的能力。我们还确定因子X主要由TF-fVIIa激活,并且大部分TF存在于精浆中,这与前列腺小体的定位一致。精液中未检测到内源性因子X,但在未添加fVIIa的情况下添加的因子X发生了激活。后续实验表明,精浆含有内源性fVII样活性,但添加更多fVIIa可增加因子X的激活。因此,虽然精浆含有大量TF,但其激活因子X的潜力受到fVII可用性和内源性因子X缺失的限制。对不育患者精液标本的评估显示TF-fVII活性存在16倍的差异。TF与禁欲天数、标本pH值、精子计数或精子活力之间没有明显关系。在用钙和离子载体A23187处理精液后,精浆中产生了独立于进一步TF活性的额外因子X激活潜力。在激活过程中添加抗TF抗体可阻断这种额外活性的产生。由于精液中不存在内源性因子X,A23187刺激产生的额外活性似乎是由于精液中TF-fVII的内源性非因子X底物。这种内源性底物可能是因子IX或TF-fVIIa的新型新底物。未来的实验将检验这些假设。