Mechanism and role of phagocytosis of unwanted cells

• Project/Area Number: 16570112
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Kanazawa University
• Principal Investigator: SHIRATSUCHI Akiko Kanazawa Univ., Grad.Sch.Med.Sci., Assistant Professor, 医学系研究科, 講師 (90303297)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
• Keywords: phagocytosis / innate immuniti / phosphatidylserine / spermatogenesis / influenza virus / scavenger receptor / insect immunity

Research Abstract

1) Mechanism and role of SR-BI-mediated apoptotic spermatogenic cells by Sertoli cells in the testis
After binding of phosphatidylserine on the surface of apoptotic cells, SR-BI in Sertoli cells induces phhosphorylation of MAP kinase p38 and ERKI/II. In the presence of inhibitors for p38-pathway and ERK-pathway, phagocytosis of apoptotic cells by Sertoli cells was inhibited greatly. These results showed that SR-BI, when it binds to phosphatidylserine, transmits signals to activate MAP kinase pathway, which leads to the induction of the engulfment of phosphatidylserine-exposing apoptotic cells by phagocytic cells.
2) Role of phagocytosis of ineluenza virus-infected cells by phagocytes
In the lung of influenza virus-infected mice, virus-infected cells were shown in both neutrophils and alveolar macrophages. Administration of the phagocytosis inhibitors into the lung caused both the lethality in mice and the extent of inflammation in the lung were augmented in those mice. These results suggest that phagocytosis of virus-infected cells helps suppress the progress of influenza in mice.
3) Regulation of phagosome-lysosome fusion
MAP kinase p38-pathway and ERK-pathway were activated in macrophages after incubation with apoptotic cells, and the activity seemed to be needed to phagosome-lysosome fusion in macrophages.

Research Products

• [Journal Article] Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes. (2006)
  • Author(s): Bayarsaikhan, M., Shiratsuchi, A., et al.
  • Journal Title: Reproduction 131 Pages: 711-719
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microslia. (2006)
  • Author(s): Zhang, J., Shiratsuchi, A., Nakanishi, Y., Nakanishi, H.et al.
  • Journal Title: J.Neuroimmunol. 172 Pages: 112-120
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes. (2006)
  • Author(s): Bayarsaikhan, M., Shiratsuchi, A., Gantulga, D., Nakanishi, Y., Yoshioka, K.
  • Journal Title: Reproduction 131 Pages: 711-719
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. (2006)
  • Author(s): Zhang, J., Fujii, S., Wu, Z., Hashioka, S., Tanaka, Y., Shiratsuchi, A., Nakanishi, Y., Nakanishi, H.
  • Journal Title: J.Neuroimmunol. 172 Pages: 112-120
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes. (2006)
  • Author(s): Bayarsaikhan, M., Shiratsuchi, A., et al.
  • Journal Title: Reproduction (in press)
• [Journal Article] Involvement of COX-1 and up-regulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. (2006)
  • Author(s): Zhang, J., Shiratsuchi, A., Nakanishi, Y., Nakanishi, H.et al.
  • Journal Title: J. Neuroimmunol. (in press)
• [Journal Article] Augumentation of fatality of influenza in mice by inhibition of phagocytosis. (2005)
  • Author(s): Watanabe, Y., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: Biochem.Biophys.Res.Commun 337 Pages: 881-886
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Isolation of Drosophila gene coding for a protein containinga novel phosphatidylserine-binding motif. (2005)
  • Author(s): Nakai, Y., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: J.Biochem. 137 Pages: 593-599
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phosphatidylserine- and integrin-mediated phagocytosis of apoptotic rat luteal cells by macrophages. (2005)
  • Author(s): Kato, S., Shiratsuchi, A., Nakanishi, Y.
  • Journal Title: Dev.Growth Differ. 47 Pages: 153-161
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells. (2005)
  • Author(s): Nakai, Y., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: Exp.Cell Res. 309 Pages: 137-148
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Distinct localization of lipid rafts and externalized phosphatidylserine at the surface of apoptotic cells. (2005)
  • Author(s): Ishii, H., Shiratsuchi.A., Nakanishi, Y.et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 327 Pages: 94-99
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells. (2005)
  • Author(s): Nakagawa, A., Shiratsuchi.A., Nakanishi, Y.et al.
  • Journal Title: Mol.Reprod.Dev. 48 Pages: 875-881
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Augumentation of fatality of influenza in mice by inhibition of phagocytosis. (2005)
  • Author(s): Watanabe, Y., Hashimoto, Y., Shiratsuchi, A., Takizawa, T., Nakanishi, Y.
  • Journal Title: Biochem.Biophys.Res.Commun. 337 Pages: 881-886
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells. (2005)
  • Author(s): Nakai, Y., Shiratsuchi, A., Manaka, J., Nakayama, H., Takio, K., Zhang, J., Nakanishi, Y.
  • Journal Title: Exp.Cell Res. 309 Pages: 137-148
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Isolation of Drosophila gene coding for a protein containinga novel phosphatidylserine-binding motif.. (2005)
  • Author(s): Nakai, Y., Nomura, Y., Sato., T., Shiratsuchi, A., Nakanishi, Y.
  • Journal Title: J.Biochem. 137 Pages: 593-599
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phosphatidylserine-and integrin-mediated phagocytosis of apoptotic rat luteal cells by macrophages. (2005)
  • Author(s): Kato, S., Shiratsuchi, A., Nakanishi, Y.
  • Journal Title: Dev.Growth Differ. 47 Pages: 153-161
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells. (2005)
  • Author(s): Nakagawa, A., Shiratsuchi, A., Nakanishi, Y.
  • Journal Title: Mol.Reprod.Dev. 71 Pages: 166-177
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Distinct localization of lipid rafts and externalized phosphatidylserine at the surface of apoptotic cells. (2005)
  • Author(s): Ishii, H., Mori, T., Shiratsuchi, A., Nakai, Y., Shimada, Y., Ohno-Iwashita, Y., Nakanishi, Y.
  • Journal Title: Biochem.Biophys.Res.Commun. 327 Pages: 94-99
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Isolation of Drosophila gene coding for a protein containinga novel phosphatidylserine-binding motif.. (2005)
  • Author(s): Nakai, Y., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: J.Biochem. 137 Pages: 593-599
• [Journal Article] Distinct localization of lipid rafts and externalized phosphatidylserine at the surface of apoptotic cells. (2005)
  • Author(s): Ishii, H., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: Biochem.Biophys.Res.Commun. (in press)
• [Journal Article] In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells. (2005)
  • Author(s): Nakagawa, A., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: Mol.Reprod.Dev. (in press)
• [Journal Article] Inhibitory effect of Toll like receptor 4 on fusion between phagosomes and endosomes/lysosomes in macrophages. (2004)
  • Author(s): Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: J.Immunol. 172 Pages: 2039-2047
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression and function of class B scavenger receptor type I on both apical and basolateral sides of the plasma membrane of polarized testicular Sertoli cells of the rat. (2004)
  • Author(s): Nakagawa, A., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: Develop.Growth Differ. 46 Pages: 283-298
  • NAID: 10013279608
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. (2004)
  • Author(s): Manaka, J., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: J.Biol.Chem. 279 Pages: 48466-48476
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stimulation of phagocytosis of influenza virus-infected cells through surface desialylation of macrophages by viral neuraminidase. (2004)
  • Author(s): Watanabe, Y., Shiratsuchi, A., Nakanishi, Y.et al.
  • Journal Title: Microbiol.Immunol 48 Pages: 875-881
  • NAID: 10014023511
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Stimulation of phagocytosis of influenza virus-infected cells through surface desialylation of macrophages by viral neuraminidase. (2004)
  • Author(s): Watanabe, Y., Shiratsuchi, A., Shimizu, K., Takenori Takizawa, T., Nakanishi, Y.
  • Journal Title: Microbiol.Immunol. 48 Pages: 875-881
  • NAID: 10014023511
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. (2004)
  • Author(s): Manaka, J., Kuraishi, T., Shiratsuchi, A., Nakai, Y., Higashida, H., Henson, P., Nakanishi, Y.
  • Journal Title: J.Biol.Chem. 279 Pages: 48466-48476
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression and function of class B scavenger receptor type I on both apical and basolateral sides of the plasma membrane of polarized testicular Sertoli cells of the rat. (2004)
  • Author(s): Nakagawa, A., Nagaosa, K., Hirose, T., Tsuda, K., Hasegawa, K., Shiratsuchi, A., Nakanishi, Y.
  • Journal Title: Develop.Growth Differ. 46 Pages: 283-298
  • NAID: 10013279608
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibitory effect of Toll like receptor 4 on fusion between phagosomes and endosomes/lysosomes in macrophages. (2004)
  • Author(s): Shiratsuchi, A., Watanabe, I., Takeuchi, O., Akira, S., Nakanishi, Y.
  • Journal Title: J.Immunol. 172 Pages: 2039-2047
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 薬学生のための細胞生物学 (2005)
  • Author(s): 堅田利明, 白土明子, 中西義信他8名
  • Total Pages: 29
  • Publisher: 廣川書店
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 薬学生のための細胞生物学 (2005)
  • Author(s): 堅田利明, 白土明子, 中西義信 他8名
  • Total Pages: 29
  • Publisher: 廣川書店