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精浆中免疫抑制活性与免疫调节细胞因子之间的关系:精子自身免疫和精浆白细胞的影响。

The relationship between immunosuppressive activity and immunoregulatory cytokines in seminal plasma: influence of sperm autoimmunity and seminal leukocytes.

作者信息

Ochsenkühn Robert, O'Connor Anne E, Hirst Jonathan J, Gordon Baker H W, de Kretser David M, Hedger Mark P

机构信息

Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Vic. 3168, Australia.

出版信息

J Reprod Immunol. 2006 Aug;71(1):57-74. doi: 10.1016/j.jri.2006.01.002. Epub 2006 May 18.

DOI:10.1016/j.jri.2006.01.002
PMID:16712948
Abstract

While the contributions of prostasomes, polyamines and prostaglandins to the immunosuppressive activity (ISA) of human seminal plasma have been well-characterised, the contribution of immunoregulatory cytokines found in seminal plasma has received relatively little attention. Semen samples were collected from adult men displaying normospermic parameters, sperm antibodies or substantially elevated seminal leukocytes. Samples were processed through ultracentrifugation and dialysis (<3500Da) to remove prostasomes, polyamines and prostaglandins, and then assayed for ISA by an in vitro T lymphocyte inhibition assay, as well as by specific immunoassays for transforming growth factor beta(1) (TGFbeta(1)), interleukin-10 (IL-10), activin A and the activin-binding protein, follistatin. Seminal plasma from all groups retained substantial ISA following processing. Compared with normospermic men, this 'large' molecular weight ISA fraction was significantly increased in a subset of men with sperm antibodies, but was not altered in the group with elevated leukocytes. There was no relationship between ISA and any cytokine examined, and only TGFbeta(1) was present at levels sufficient to contribute to ISA. Inhibition with a TGFbeta-specific antibody reduced ISA in seminal plasma by approximately 50%. Across all patients, TGFbeta(1) levels were positively correlated with sperm numbers in the ejaculate and with activin A, but not with follistatin or IL-10. Activin A and IL-10 also displayed a positive relationship, and elevated leukocytes was associated with a significant elevation of IL-10 and activin A, but not TGFbeta(1). It is concluded that 'large' molecular weight molecules, the most important of which appears to be TGFbeta(1), make a significant contribution to immunosuppression by human seminal plasma.

摘要

虽然前列腺小体、多胺和前列腺素对人类精浆免疫抑制活性(ISA)的作用已得到充分表征,但精浆中发现的免疫调节细胞因子的作用却相对较少受到关注。从精液参数正常、有精子抗体或精浆白细胞显著升高的成年男性中采集精液样本。样本经超速离心和透析(<3500Da)处理以去除前列腺小体、多胺和前列腺素,然后通过体外T淋巴细胞抑制试验以及针对转化生长因子β(1)(TGFβ(1))、白细胞介素-10(IL-10)、激活素A和激活素结合蛋白卵泡抑素的特异性免疫测定来检测ISA。所有组的精浆在处理后仍保留大量的ISA。与精液参数正常的男性相比,这种“大”分子量的ISA部分在一部分有精子抗体的男性中显著增加,但在白细胞升高的组中没有变化。ISA与所检测的任何细胞因子之间均无关联,只有TGFβ(1)的水平足以对ISA产生影响。用TGFβ特异性抗体抑制可使精浆中的ISA降低约50%。在所有患者中,TGFβ(1)水平与射精中的精子数量以及激活素A呈正相关,但与卵泡抑素或IL-10无关。激活素A和IL-10也呈正相关,白细胞升高与IL-10和激活素A的显著升高相关,但与TGFβ(1)无关。得出的结论是,“大”分子量分子,其中最重要的似乎是TGFβ(1),对人类精浆的免疫抑制作用有显著贡献。

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