Laboratory of Molecular and Cellular Biochemistry,
Grad. Sch. Med. Sci., Kanazawa University
as of January 2012
I. Mechanism of Phagocytosis of Unwanted Cells for Morphogenesis and Tissue Functions
1) Recognition of apoptotic cells by phagocytes in Drosophila
Manaka, J., Kuraishi, T., Shiratsuchi, A., Nakai, Y., Higashida, H., Henson, P., and Nakanishi, Y.: Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. J. Biol. Chem. 279, 48466-48476 (2004)
Kuraishi, T., Manaka, J., Kono, M., Ishii, H., Yamamoto, N., Koizumi, K., Shiratsuchi, A., Lee, B. L., Higashida, H., and Nakanishi, Y.: Identification of calreticulin as a marker for phagocytosis of apoptotic cells in Drosophila. Exp. Cell Res. 313, 500-510 (2007)
Kuraishi, T., Nakagawa, Y., Nagaosa, K., Hashimoto, Y., Ishimoto, T., Moki, T., Fujita, Y., Nakayama, H., Dohmae, N., Shiratsuchi, A., Yamamoto, N., Ueda, K., Yamaguchi, M., Awasaki, T., and Nakanishi, Y.: Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells. EMBO J. 28, 3668-3878 (2009)
Nagaosa, K., Okada, R., Nonaka, S., Takeuchi, K., Fujita, Y., Miyasaka, T., Manaka, J., Ando, I., and Nakanishi, Y.: Integrin betanu-mediated phagocytosis of apoptotic cells in Drosophila. J. Biol. Chem. 286, 25770-25777.
Okada, R., Nagaosa, K., Kuraishi, Y., Nakayama, H., Yamamoto, N., Nakagawa, Y., Dohmae, N., Shiratsuchi, A., and Nakanishi, Y.: Apoptosos-dependent externalization and involvement in apoptotic cell clearance of DmCaBP1, an endoplasmic reticulum protein of Drosophila. J. Biol. Chem. in press
2) Phagocytosis of PS-exposing cells by macrophages
Shiratsuchi, A., Osada, S., Kanazawa, S., and Nakanishi, Y.: Essential role of phosphatidylserine externalization in apoptosing cell phagocytosis by macrophages. Biochem. Biophys. Res. Commun. 246, 549-555 (1998)
Shiratsuchi, A., and Nakanishi, Y.: Phosphatidylserine-mediated phagocytosis of anticancer drug-treated cells by macrophages. J. Biochem. 126, 1101-1106 (1999)
3) Search for novel phagocytosis markers
Fujii, C., Shiratsuchi, A., Manaka, J., Yonehara, S., and Nakanishi, Y.: Difference in the way of macrophage recognition of target cells depending on their apoptotic states. Cell Death Differ. 8, 1113-1122 (2001)
Nishida, J., Shiratsuchi, A., Nadano, D., Sato, T., and Nakanishi, Y.: Structural change of ribosomes during apoptosis: degradation and translocation of ribosomal proteins in doxorubicin-treated Jurkat cells. J. Biochem. 131, 485-493 (2002)
Shiratsuchi A., Mori, T., and Nakanishi, Y.: Independence of plasma membrane blebbing from other biochemical and biological characteristics of apoptotic cells. J. Biochem. 132, 381-386 (2002)
Shiratsuchi, A., Mori, T., Takahashi, Y., Sakai, K., and Nakanishi, Y.: A presumed human nuclear autoantigen that translocates to plasma membrane blebs duing apoptosis. J. Biochem. 133, 211-218 (2003)
Ishii, H., Mori, T., Shiratsuchi, A., Nakai, Y., Shimada, Y., Ohno-Iwashita, Y., and Nakanishi, Y.: Distinct localization of lipid rafts and externalized phosphatidylserine at the surface of apoptotic cells. Biochem. Biophys. Res. Commun. 327, 94-99 (2005)
Nakai, Y., Nomura, Y., Sato., T., Shiratsuchi, A., Suganuma, T., and Nakanishi, Y.: Isolation of Drosophila gene coding for a protein containing a novel phosphatidylserine-binding motif. J. Biochem. 137, 593-599 (2005)
Nakai, Y., Shiratsuchi, A., Manaka, J., Nakayama, H., Takio, K., Zhang, J., and Nakanishi, Y.: Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells. Exp. Cell Res. 309, 137-148 (2005)
Hashimoto, Y., Tabuchi, Y., Sakurai, K., Kutsuna, M., Kurokawa, K., Awasaki, T., Sekimizu, K., Nakanishi, Y., and Shiratsuchi, A.: Identification of lipoteichoic acid as a ligand for Draper in the phagocytosis of Stapylococcus aureus by Drosophila hemocytes. J. Immunol. 183, 7451-7460 (2009)
Kuraishi, T., Nakagawa, Y., Nagaosa, K., Hashimoto, Y., Ishimoto, T., Moki, T., Fujita, Y., Nakayama, H., Dohmae, N., Shiratsuchi, A., Yamamoto, N., Ueda, K., Yamaguchi, M., Awasaki, T., and Nakanishi, Y.: Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells. EMBO J. 28, 3668-3878 (2009)
II. Mechanism of Phagocytosis of Microbes and Microbe-Infected Cells to Prevent Infections
1) Regulation of phagocytic elimination of microbes by macrophages/neutrophils or Drosophila hemocytes
Shiratsuchi, A., Watanabe, I., Takeuchi, O., Akira, S., and Nakanishi, Y.: Inhibitory effect of Toll like receptor 4 on fusion between phagosomes and endosomes/lysosomes in macrophages. J. Immunol. 172, 2039-2047 (2004)
Watanabe, I., Ichiki, M., Shiratsuchi, A., and Nakanishi, Y.: Tlr2-mediated survival of Staphylococcus aureus in macrophages: a novel bacterial strategy against host innate immunity. J. Immunol. 178, 4917-4925 (2007) Picked up in the “IN THIS ISSUE”
Hashimoto, Y., Moki, T., Takizawa, T., Shiratsuchi, A., and Nakanishi, Y.: Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J. Immunol. 178, 2448-2457 (2007) Selected by “Faculty of 1000 Biology, Immunology Section”
Shiratsuchi, A., Watanabe, I., Yoshida, H., and Nakanishi, Y.: Involvment of cannabinoid receptor CB2 in dectin-1-mediated macrophage phagocytosis. Immunol. Cell Biol. 86, 179-184 (2008)
Shiratsuchi, A., Watanabe, I., Ju, J.-S., Lee, B.-L., and Nakanishi, Y.: Bridging effect of recombinant human mannose-binding lectin in macrophage phagocytosis of Eschericha coli. Immunology 124, 575-583 (2008)
Shiratsuchi, A., Ichiki, M., Okamoto, Y., Ueda, N., Sugimoto, N., Takuwa, Y., and Nakanishi, Y.: Inhibitory effect of N-palmitoylphosphatidylethanolamine on macrophage phagocytosis through inhibitio of Rac1 and Cdc42. J. Biochem. 145, 43-50 (2009)
Hashimoto, Y., Tabuchi, Y., Sakurai, K., Kutsuna, M., Kurokawa, K., Awasaki, T., Sekimizu, K., Nakanishi, Y., and Shiratsuchi, A.: Identification of lipoteichoic acid as a ligand for Draper in the phagocytosis of Stapylococcus aureus by Drosophila hemocytes. J. Immunol. 183, 7451-7460 (2009)
Shiratsuchi, A., Shimizu, K., Watanabe, I., Hashimoto, Y., Kurokawa, K., Razanajatovo, I. M., Park, K. H., Park H. K., Lee, B. L., Sekimizu, K., and Nakanishi, Y.: Auxiliary role for D-alanylated wall teichoic acid in Toll-like receptor 2-mediated survival of Staphylococcus aureus in macrophages. Immunololgy 129, 268-277 (2010)
Tabuchi, Y., Shiratsuchi, A., Kurokawa, K., Gong, J. H., Sekimizu, K., Lee, B. L., and Nakanishi, Y.: Inhibitory role for D-alanylation of wall teichoic acid in activatino of insect Toll pathway by peptidoglycan of Staphylococcus aureus. J. Immunol. 185, 2424-2431 (2010)
2) Phagocytosis of influenza virus-infected cells by macrophages
Takizawa, T., Matsukawa, S., Higuchi, Y., Nakamura, S., Nakanishi, Y., and Fukuda, R.: Induction of programmed cell death (apoptosis) by influenza virus infection in tissue cultured cells. J. Gen. Virol. 74, 2347-2355 (1993)
Takizawa, T., Fukuda, R., Miyawaki, T., Ohashi, K., and Nakanishi, Y.: Activation of the apoptotic Fas antigen-encoding gene upon influenza virus infection involving spontaneously produced beta-interferon. Virology 209, 288-296 (1995)
Wada, N., Matsumura, M., Ohba, Y., Kobayashi, N., Takizawa, T., and Nakanishi, Y.: Transcription stimulation of the Fas-encoding gene by nuclear factor for interleukin-6 expression upon influenza virus infection. J. Biol. Chem. 270, 18007-18012 (1995)
Takizawa, T., Ohashi, K., and Nakanishi, Y.: Possible involvement of double-stranded RNA-activated protein kinase (PKR) in the cell death by influenza virus infection. J. Virol. 70, 8128-8132 (1996)
Fujimoto, I., Takizawa, T., Ohba, Y., and Nakanishi, Y.: Co-expression of Fas and Fas-ligand on the surface of influenza virus-infected cells. Cell Death Differ. 5, 426-431 (1998)
Takizawa, T., Tatematsu, C., Ohashi, K., and Nakanishi, Y.: Recruitment of apoptotic cysteine proteases (caspases) in influenza virus-induced cell death. Microbiol. Immunol. 43, 245-252 (1999)
Fujimoto, I., Pan, J., Takizawa, T., and Nakanishi, Y.: Virus clearance through apoptosis-dependent phagocytosis of influenza A virus-infected cells by macrophages. J. Virol. 74, 3399-3403 (2000)
Shiratsuchi, A., Kaido, M., Takizawa, T., and Nakanishi, Y.: Phosphatidylserine-mediated phagocytosis of influenza A virus-infected cells by mouse peritoneal macrophages. J. Virol. 74, 9240-9244 (2000)
Watanabe, Y., Shiratsuchi, A., Shimizu, K., Takizawa, T., and Nakanishi, Y.: Role of phosphatidylserine exposure and sugar chain desialylation at the surface of influenza virus-infected cells in efficient phagocytosis by macrophages J. Biol. Chem. 277, 18222-18228 (2002)
Watanabe,Y., Shiratsuchi, A., Shimizu, K., Takizawa, T., and Nakanishi, Y.: Stimulation of phagocytosis of influenza virus-infected cells through surface desialylation of macrophages by viral neuraminidase. Microbiol. Immunol. 48, 875-881 (2004)
Watanabe,Y., Hashimoto, Y., Shiratsuchi, A., Takizawa, T., and Nakanishi, Y.: Augmentation of fatality of influenza in mice by inhibition of phagocytosis. Biochem. Biophys. Res. Commun. 337, 881-886 (2005)
Hashimoto, Y., Moki, T., Takizawa, T., Shiratsuchi, A., and Nakanishi, Y.: Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice. J. Immunol. 178, 2448-2457 (2007) Selected by “Faculty of 1000 Biology, Immunology Section”
3) Regulation of immune response to microbes by macrophages or epithelium
Nagaosa, K., Nakashima, C., Kishimoto, A., and Nakanishi, Y.: Immune response to bacteria in seminiferous epithelium. Reproduction 137, 879-888 (2009)
III. Mechanism of Phagocytosis of Unwanted Cells for Regulation of Gamete Production
1) Phagocytosis of apoptotic spermatogenic cells by testicular Sertoli cells
Mizuno, K., Shiratsuchi, A., Masamune, Y., and Nakanishi, Y.: The role of Sertoli cells in the differentiation and exclusion of rat testicular germ cells in primary culture. Cell Death Differ. 3, 119-123 (1996)
Shiratsuchi, A., Umeda, M., Ohba, Y., and Nakanishi, Y.: Recognition of phosphatidylserine on the surface of apoptotic spermatogenic cells and subsequent phagocytosis by Sertoli cells of the rat. J. Biol. Chem. 272, 2354-2358 (1997)
Shiratsuchi, A., Kawasaki, Y., Ikemoto, M., Arai, H., and Nakanishi, Y.: Role of class B scavenger receptor type I in phagocytosis of apoptotic rat spermatogenic cells by Sertoli cells. J. Biol. Chem. 274, 5901-5908 (1999)
Koji, T., Hishikawa, Y., Ando, H., Nakanishi, Y., and Kobayashi, N.: Expression of Fas and Fas ligand in normal and ischemia-reperfusion testes: involvement of the Fas system in the induction of germ cell apoptosis in the damaged mouse testis. Biol. Reprod. 64, 946-954 (2001)
Maeda, Y., Shiratsuchi, A., Namiki, M., and Nakanishi, Y.: Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Cell Death Differ. 9, 742-749 (2002)
Kawasaki, Y., Nakagawa, A., Nagaosa, K., Shiratsuchi, A., and Nakanishi, Y.: Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular Sertoli cells. J. Biol. Chem. 277, 27559-27566 (2002)
Nakagawa, A., Nagaosa, K., Hirose, T., Tsuda, K., Hasegawa, K., Shiratsuchi, A., and Nakanishi, Y.: 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. Develop. Growth Differ. 46, 283-298 (2004)
Nakagawa, A., Shiratsuchi, A., Tsuda, K., and Nakanishi, Y.: In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells. Mol. Reprod. Dev. 71, 166-177 (2005)
Osada, Y., Shiratsuchi, A., and Nakanishi, Y.: Involvement of mitogen-activated protein kinases in class B scavenger receptor type I-induced phagocytosis of apoptotic cells. Exp. Cell Res. 312, 1820-1830 (2006)
Nagaosa, K., Kishimoto, A., Kizu, R., Nakagawa, A. Shiratsuchi, A., and Nakanishi, Y.: Perturbation of spermatogenesis by androgen antagonists directly injected into seminiferous tubules of live mice. Reproduction 133, 21-27 (2007)
Osada, Y., Sunatani, T., Kim, I.-S., Nakanishi, Y., and Shiratsuchi, A.: Signaling pathway involving GULP, MAPK, and Rac1 for SR-BI-induced phagocytosis of apoptotic cells. J. Biochem. 145, 587-394 (2009)
2) Migration of macrophages to regressive corpora lutea
Nagaosa, K., Shiratsuchi, A., and Nakanishi, Y.: Determination of cell type specificity and estrous cycle dependency of monocyte chemoattractant protein-1 expression in corpora lutea of normally cycling rats in relation to apoptosis and monocyte/macrophage accumulation. Biol. Reprod. 67, 1502-1508 (2002)
Nagaosa, K., Shiratsuchi, A., and Nakanishi, Y.: Concomitant induction of apoptosis and expression of monocyte chemoattractant protein 1 in cultured rat luteal cells by nuclear factor-kappa B and oxidative stress. Develop. Growth Differ. 45, 351-359 (2003)
Kato, S., Shiratsuchi, A., Nagaosa, K., and Nakanishi, Y.: Phosphatidylserine- and integrin-mediated phagocytosis of apoptotic rat luteal cells by macrophages. Develop. Growth Differ. 47, 153-161 (2005)
Nagaosa, K., Aikoshi, I., Hasegawa, Y., and Nakanishi, Y. Activator protein 1-mediated expression of monocyte chemoattractant protein 1 in cultured rat luteal cells. Mol. Reprod. Dev. 75, 1077-1084 (2008)
Reviews and Book chapters
Nakanishi, Y., Nagaosa, K., and Shiratsuchi, A.: (review) Phagocytic removal of cells that have become unwanted: inplications for animal development and tissue homeostasis. Develop. Growth Differ. 53, 149-160 (2011)
Takizawa, T., and Nakanishi, Y.: (review) Role and pathological significance of apoptosis induced by influenza virus infections. The Open Antimicrobial Agents Journal 2, 22-25 (2010)
Shiratsuchi, A. and Nakanishi, Y.: (review) Mentenance of tissue homeostasis by apoptosis-dependent phagocytosis. Experimental Medicine 28, 1055-1031 (2010)
Nakanishi, Y., Henson, P. M., and Shiratsuchi, A.: (review) Pattern recognition in phagocytic clearance of altered self. Adv. Exp. Med. Biol. 653, 129-138 (2009)
Shiratsuchi, A., and Nakanishi, Y. (review) Phospholipid-mediated phagocytic elimination of apoptotic cells. Oleo Science 9, 465-471 (2009)
Shiratsuchi, A.: (review) Study on the mechamism and role of phagocytic elimination of microbes and microbe-infected cell. J. Juzen Med. Soc. 118, 9-12 (2009)
Nakanishi, Y., Hashimoto, Y., Takizawa, T., and Shiratsuchi, A. (review) Mechanisms and consequences of phagocytosis of influenza virus-infected cells. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 7, 97-100 (2008)
Nakanishi, Y., and Shiratsuchi, A.: (review) Mechanisms and roles of phagocytosis in Drosophila and Caenorhabditis elegans. Invert. Surviv. J. 3, 89-96 (2006)
Nakanishi, .Y.: (review) Regulation of apoptosis in virus-infected cells. Tiss. Cult. Res. Commun. 14, 127-132 (1995)
Nakanishi, Y., Shiratsuchi, A., and Takizawa, T.: (book chapter) Mechanism and physiological role of apoptosis induction in influenza virus-infected cells. in Recent Advances in Influenza Virus Research, Hayase, Y., ed., Research Signpost, 37: 661 (2), 56-61 (2002)
Nakanishi, Y., and Shiratsuchi, A.: (review) Phagocytic removal of apoptotic spermatogenic cells by Sertoli cells: mechanisms and consequences. Biol. Pharm. Bull. 27, 13-16 (2004)
Original Articles (Collaboration)
Wu, Z., Ma, H. M., Kukita, T., Nakanishi, Y., and Nakanishi, H.: Phosphatidylserine-containing liposomes inhibit the differentiation of osteoclasts and trabecular bone loss. J. Immunol. 184, 3191-3201 (2010) collaboration with Dr. Nakanishi, H. (Kyushu Univ., Japan)
Kurokawa, K., Lee, H., Rho, K.-B., Asanuma, M., Kim, Y.S., Nakayama, H., Shiratsuchi, A., Choi, Y., Takeuchi, O., Kang, H.J., Dohmae, N., Nakanishi, Y., Akira, S., Sekimizu, K., and Lee, B.-L.: The triacylated ATP binding cluster transporter substrate-binding lipoprotein of Staphylococcus aureus functions as a native ligand for the Toll-like receptor 2. J. Biol. Chem. 284, 8406-8411 (2009) collaboration with Dr. Lee, B.L. (Pusan Nat. Univ., Korea)
Kakishima, K., Shiratsuchi, A., Taoka, A., Nakanishi, Y., and Fukumori, Y.: Participation of nitric oxide reductase in survival of Pseudomonas aeruginosa in LPS-activated macrophages. Biochem. Biophys. Res. Commun. 355, 587-591 (2007) collaboration with Dr. Fukumori, Y. (Kanazawa Univ., Japan)
Nagaosa, K., Kishimoto, A., Kizu, R., Nakagawa, A. Shiratsuchi, A., and Nakanishi, Y.: Perturbation of spermatogenesis by androgen antagonists directly injected into seminiferous tubules of live mice. Reproduction 133, 21-27 (2007) collaboration with Dr. Kizu, R. (Kanazawa Univ., Japan)
Awasaki, T., Tatsumi, R., Takahashi, K., Arai, K., Nakanishi, Y., Ueda, R., and Ito K.: Essential role of the apoptotic cell engulfment genes draper and ced-6 in developmentally programmed axon pruning during Drosophila metamorphosis. Neuron 50, 855-867 (2006) collaboration with Dr. Awasaki, T. (Univ. Massachusetts, USA)
Bayarsaikhan, M., Shiratsuchi, A., Gantulga, D., Nakanishi, Y., and Yoshioka, K.: Selective expression of the scaffold protein JSAP1 in spermatogonia and spermatocytes. Reproduction 131, 711-719 (2006) collaboration with Dr. Yoshioka, K. (Kanazawa Univ., Japan)
Zhang, J., Fujii, S., Wu, Z., Hashioka, S., Tanaka, Y., Shiratsuchi, A., Nakanishi, Y., and Nakanishi, H.: Involvement of COX-1 and up-regtulated prostaglandin E synthases in phosphatidylserine liposome-induced prostaglandin E2 production by microglia. J. Neuroimmunol. 172, 112-120 (2006) collaboration with Dr. Nakanishi, H. (Kyushu Univ., Japan)
Nakamoto, T., Shiratsuchi, A., Oda, H., Matsumura, T., Ichikawa, M., Saito, T., Seo, S., Maki, K., Asai, T., Suzuki, T., Yamagata, T., Aizawa, S., Noda, M., Nakanishi, Y., and Hirai, H.: Impairment of spermatogenesis and male fertility in CIZ/Nmp4-disrupted mice. Genes Cells 9, 575-589 (2004) collaboration with Drs. Nakamoto, T., and Hirai, H. (Univ. Tokyo., Japan)