FUNCTIONALLY ACTIVE PROTEIN-C INHIBITOR PLASMINOGEN-ACTIVATOR INHIBITOR-3 (PCI/PAI-3) IS SECRETED IN SEMINAL-VESICLES, OCCURS AT HIGH-CONCENTRATIONS IN HUMAN SEMINAL PLASMA AND COMPLEXES WITH PROSTATE-SPECIFIC ANTIGEN

FUNCTIONALLY ACTIVE PROTEIN-C INHIBITOR PLASMINOGEN-ACTIVATOR INHIBITOR-3 (PCI/PAI-3) IS SECRETED IN SEMINAL-VESICLES, OCCURS AT HIGH-CONCENTRATIONS IN HUMAN SEMINAL PLASMA AND COMPLEXES WITH PROSTATE-SPECIFIC ANTIGEN
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DOI:
10.1016/0049-3848(91)90002-e
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发表时间:
1991-11-01
影响因子:
7.5
通讯作者:
CABO, A
CABO, A
中科院分区:
医学3区
文献类型:
--
作者:
ESPANA, F;GILABERT, J;CABO, A

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蛋白C抑制剂(PCI)是一种肝素依赖性丝氨酸蛋白酶抑制剂,以天然形式存在于血浆中,浓度为5 μ g/mL。 在体外,PCI抑制活化蛋白C(APC),凝血酶,血浆激肽释放酶(KK)和尿激酶-(uPA)和组织型纤溶酶原激活剂(tPA),我们已经表明,在体内抑制APC,uPA和KK的PCI。 为了进一步表征PCI的生理作用,我们测量了几种生物体液中PCI的水平。 PCI抗原通过ELISA测定,PCI活性通过其在肝素存在下与APC形成复合物的能力来测量。 来自自愿捐献者的精浆的PCI水平(160 +/- 20 μ g/mL,平均值+/- SD)比血浆中发现的高约30或40倍。 接受受精程序的患者PCI精液水平显著降低(110 +/- 35 μ g/mL)。 精浆PCI保留约45%的活性后,立即射精,和活动迅速下降后孵育的精浆在37 ℃,在平行的PCI与前列腺特异性抗原(PSA)的复合物的外观。 PCI存在于精囊分泌物中,通过尸检获得,浓度与精液中观察到的浓度相似,主要是活性的,并且在37 ℃下孵育分泌物时不会灭活。 正常供体尿液中PCI的平均功能和抗原水平分别为0.58和0.25 μ g/mL,而唾液中这些水平分别为20和0.8 ng/mL。 羊水含有2.1 +/- 0.2 μ g/mL的PCI抗原水平。 这些结果表明,PCI是分泌在精囊中的功能形式,并建议PSA,前列腺的主要分泌成分,是负责其失活。 他们还提出了PCI在生殖中的生理作用,并表明PCI存在于各种生物液体中。
Protein C inhibitor (PCI) is a heparin-dependent serpin present in a native form in plasma at concentrations of 5-mu-g/mL. In vitro, PCI inhibits activated protein C (APC), thrombin, plasma kallikrein (KK) and urokinase- (uPA) and tissue-type plasminogen activator (tPA), and we have shown in vivo inhibition of APC, uPA and KK by PCI. In order to further characterize the physiological role of PCI, we have measured the level of PCI in several biological fluids. PCI antigen was assayed by ELISA and PCI activity was measured by its capability to form complexes with APC in the presence of heparin. Seminal plasma from voluntary donors had PCI levels (160 +/- 20-mu-g/mL, mean +/- SD) about 30 or 40 times higher than those found in blood plasma. Patients under a fertilization program had significantly reduced PCI seminal levels (110 +/- 35-mu-g/mL). Seminal plasma PCI retained about 45% of its activity immediately after ejaculation, and the activity rapidly decreased following incubation of seminal plasma at 37-degrees-C, in parallel with the appearance of complexes of PCI with prostate-specific antigen (PSA). PCI was present in seminal vesicle secretion, obtained by autopsy, at concentration similar to that observed in semen, was mostly active and was not inactivated by incubation of secretion at 37-degrees-C. The mean functional and antigen levels of PCI in urine from normal donors were 0.58 and 0.25-mu-g/mL, respectively, whereas in saliva these levels were 20 and 0.8 ng/mL, respectively. Amniotic fluid contained PCI antigen levels of 2.1 +/- 0.2-mu-g/mL. These results show that PCI is secreted in the seminal vesicles in a functional form, and suggest that PSA, a major secretory component of the prostate, is responsible for its inactivation. They also suggest a physiological role of PCI in reproduction, and show that PCI is present in various biological fluids.