Class B scavenger receptor type I (SR-BI) is a phosphatidylserine (PS)-recognizing receptor of testicular Sertoli cells responsible for the phagocytosis of spermatogenic cells undergoing apoptosis. Here, we determined signal mediators that compose a signalling pathway for SR-BI-induced phagocytosis. Results of a yeast twohybrid analysis and a cell-free binding assay indicated that SR-BI binds to engulfment adapter protein (GULP) using the C-terminal intracellular domain. A co-immunoprecipitation analysis showed the existence of a complex of GULP and SR-BI in cells prior to the activation of SR-BI by PS. A reduction of GULP expression in phagocytes decreased the SR-BI-mediated phagocytosis of apoptotic cells. Administration to phagocytes of PS-containing liposomes increased the levels of the GTP-bound form of Rac1 and the phosphorylated forms of mitogen-activated protein kinases (MAPK) p38 and extracellular signal-related kinase 1 and 2. Finally, lowering the expression of GULP abrogated MAPK phosphorylation, and the presence of MAPK inhibitors reduced the level of GTP-bound Rac1 in PS-activated phagocytes. These results collectively suggested the following signalling pathway for the SR-BI-induced phagocytosis: (i) PS-recognizing SR-BI activates associated GULP; (ii) activated GULP induces MAPK phosphorylation; (iii) activated MAPK increases GTP-bound Rac1; and (iv) activated Rac1 induces a rearrangement of the actin cytoskeleton.
Sertoli cells, the sole somatic cell type in the seminiferous epithelium, play an essential role in spermatogenesis and spermiogenesis by nursing germ cells for their survival and differentiation as well as physically inhibiting the entrance of harmful substances into the seminiferous tubules. Sertoli cells possess the characteristics of immune cells; they express pattern recognition receptors, secrete antimicrobial proteins, and engulf dead or dying cells. In this study, we determined the mechanism by which Sertoli cells engulf and kill bacteria compared to that of macrophages. When the primary cultured Sertoli cells of rats were incubated with Staphylococcus aureus, they produced the mRNA of neutrophil protein 3, an antimicrobial peptide of the α-defensin family, but not superoxide or nitric oxide, in contrast to mouse peritoneal macrophages. Sertoli cells effectively phagocytosed S. aureus in a manner that was accompanied by cytoskeleton rearrangement and dependent on phosphatidylinositol 3-kinase. Engulfed bacteria appeared to stay alive in Sertoli cells, while they were rapidly killed in macrophages. These results collectively suggest that Sertoli cells eliminate bacteria that have invaded the seminiferous epithelium without evoking inflammation, unlike macrophages.
Metal responsive transcription factor-1 (MTF-1) is ubiquitously expressed in various tissues, and is thought to be an intracellular zinc sensor that regulates transcriptional activation of zinc responsive genes. We investigated the distribution of MTF-1 in the mouse testis, where zinc plays an essential role in spermatogenesis. By performing immunohistochemical analysis of the ddY mouse testis using the anti-MTF-1 antibody, we observed a donut-shaped staining pattern in the seminiferous tubules in the region proximal to the lumen, where spermatocytes primarily localize. A similar staining pattern was obtained using in situ hybridization to detect MTF-1 mRNA. Furthermore, we confirmed that MTF-1 could not be detected at both the protein and mRNA levels in the premature 20-d-old mouse testis, where spermatocytes are thought not to have been formed in the seminiferous tubules yet. These lines of evidence strongly indicated the selective expression of MTF-1 in mouse spermatocytes and suggested that MTF-1 played a role in a certain stage of spermatogenesis.
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