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男性生殖道中的分泌型白细胞蛋白酶抑制剂:人精液中前列腺特异性抗原诱导的蛋白水解加工及组织定位

Secretory leucocyte protease inhibitor in the male genital tract: PSA-induced proteolytic processing in human semen and tissue localization.

作者信息

Ohlsson K, Bjartell A, Lilja H

机构信息

Department of Surgical Pathophysiology, Lund University, Malmö General Hospital, Sweden.

出版信息

J Androl. 1995 Jan-Feb;16(1):64-74.

PMID:7539415
Abstract

Secretory leucocyte protease inhibitor, SLPI, is a low-molecular-weight, acid-stable protein present in the liquid part of fresh human ejaculate but not demonstrable in the gel structure. No fragmentation of SLPI occurred during gel dissolution, but a slow proteolytic cleavage of SLPI was seen on incubation of the liquified semen at 37 degrees C. The same pattern of degradation products was seen after incubation of SLPI with prostatic secretion and also with purified prostate-specific antigen, PSA. We could identify Arg 20-Tyr 21 and Met 73-Leu 74 to be the primary cleavage sites upon proteolytic modification of SLPI by purified PSA. However, we did not find any inhibition of the enzymatic activity of PSA by SLPI, even at a 100-fold molar excess of the inhibitor. The slow degradation of SLPI facilitated sampling and the reliable determination of the normal level of SLPI in seminal plasma, which was about 20 mg/L. We investigated the glandular origin of SLPI in the genital tract by immunocytochemistry. A strong immunostaining for SLPI was demonstrated in epithelial cells within the glandular lumina of the prostate gland, seminal vesicles, and epididymis but not in the stromal parts of these glands. In addition the immunostaining was also detected in the deferent ducts and the germinal epithelium of the testes. Taking into account that SLPI is a strong inhibitor of several proteases, including leukocyte elastase and cathepsin G, the results suggest that SLPI has a local protective function against proteolytic degradation of the male reproductive tract tissues during inflammation.

摘要

分泌型白细胞蛋白酶抑制剂(SLPI)是一种低分子量、酸稳定的蛋白质,存在于新鲜人类精液的液体部分,但在凝胶结构中无法检测到。在凝胶溶解过程中,SLPI没有发生片段化,但在37℃孵育液化精液时,可观察到SLPI的缓慢蛋白水解裂解。将SLPI与前列腺分泌物以及纯化的前列腺特异性抗原(PSA)一起孵育后,也观察到了相同的降解产物模式。我们可以确定,在纯化的PSA对SLPI进行蛋白水解修饰时,Arg 20-Tyr 21和Met 73-Leu 74是主要的裂解位点。然而,即使抑制剂的摩尔过量达100倍,我们也未发现SLPI对PSA的酶活性有任何抑制作用。SLPI的缓慢降解便于采样,并可靠地测定精浆中SLPI的正常水平,该水平约为20 mg/L。我们通过免疫细胞化学研究了生殖道中SLPI的腺体来源。在前列腺、精囊和附睾腺腔内的上皮细胞中,SLPI呈现强烈的免疫染色,但在这些腺体的间质部分未观察到。此外,在输精管和睾丸的生精上皮中也检测到了免疫染色。鉴于SLPI是几种蛋白酶(包括白细胞弹性蛋白酶和组织蛋白酶G)的强效抑制剂,这些结果表明,SLPI在炎症期间对男性生殖道组织的蛋白水解降解具有局部保护作用。

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