Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction
Perforin-independent expression of granzyme B and proteinase inhibitor 9 in human testis and placenta suggests a role for granzyme B-mediated proteolysis in reproduction
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DOI：
10.1093/molehr/7.12.1133
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发表时间：
2001-12-01
影响因子：
4
通讯作者：
Bird, PI
中科院分区：
文献类型：
--
作者：
Hirst, CE;Buzza, MS;Bird, PI
颗粒酶B（Granzyme B，graB）通过切割靶细胞内的蛋白质，在细胞毒性淋巴细胞颗粒介导的细胞凋亡中发挥关键作用。蛋白酶抑制剂-9（PI-9）是graB的有效抑制剂，并且在细胞毒性淋巴细胞中高度表达。在这里，我们通过免疫组化显示PI-9也在人睾丸支持细胞和胎盘合胞滋养层细胞中大量表达。假设PI-9保护这些组织免受产生graB的自身或同种异体反应性细胞毒性淋巴细胞的侵害，我们还对graB切片进行了染色。出乎意料的是，在两种组织的非细胞毒性细胞中均观察到graB。在成年人睾丸中，graB存在于生精小管内的生精细胞中，这是通过原位杂交和逆转录-聚合酶链反应（RT-PCR）验证的。足月胎盘的免疫组化分析表明graB在合胞体滋养细胞中，这一点通过RT-PCR在足月胎盘的初级滋养细胞中得到证实。穿孔素，这是与graB由活化的细胞毒性淋巴细胞和所需的graB释放到靶细胞，没有检测到睾丸或胎盘。我们假设，在这些器官中，graB具有穿孔素独立的作用，涉及细胞外基质成分的水解。在睾丸中，graB可能促进发育中的生殖细胞的迁移，而在胎盘中，它可能有助于分娩期间的细胞外基质重塑。
Granzyme B (graB) plays a pivotal role in cytotoxic lymphocyte granule-mediated apoptosis through cleavage of intracellular proteins in target cells. Proteinase inhibitor-9 (PI-9) is a potent inhibitor of graB and is highly expressed in cytotoxic lymphocytes. Here, we show by immunohistochemistry that PI-9 is also abundantly expressed in human testicular Sertoli cells and placental syncytial trophoblasts. Postulating that PI-9 protects these tissues from graB-producing auto- or allo-reactive cytotoxic lymphocytes, we also stained sections for graB. Unexpectedly, graB was observed in non-cytotoxic cells in both tissues. In the adult human testis, graB was present in spermatogenic cells within the seminiferous tubule, and this was verified by in-situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical analysis of term placentae demonstrated graB in syncytial trophoblasts, and this was confirmed by RT-PCR on primary trophoblasts from term placenta. Perforin, which is co-produced with graB by activated cytotoxic lymphocytes and is required for graB release into the target cell, was not detected in either testis or placenta. We postulate that, in these organs, graB has a perforin-independent role, involving hydrolysis of extracellular matrix components. In the testis, graB may facilitate migration of developing germ cells, while in the placenta, it may contribute to extracellular matrix remodelling during parturition.