Molecular Human Reproduction, Vol. 7, No. 12, 1133-1142,
December 2001
© 2001 European Society of Human Reproduction and Embryology
Testis and spermatogenesis |
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
1 Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, 2 The Peter MacCallum Institute, East Melbourne, 3002 and 3 Monash Institute of Reproduction and Development, Monash University, Clayton, 3168, Australia
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.
extracellular matrix remodelling/granzyme B/perforin/proteinase inhibitor 9 (PI-9)/serpin
4 To whom correspondence should be addressed at: Department of Biochemistry and Molecular Biology, Building 13B, Room G09, Monash University, Clayton, 3800, Australia. E-mail: phil.bird{at}med.monash.edu.au
* Both authors contributed equally to this work
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