Grad. Sch. Med. Sci., Kanazawa Univ., Shizenken, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan

As of September, 2009.

Yoshinobu Nakanishi, Ph.D., professor

Akiko Shiratsuchi, Ph.D., associate professor

Kaz Nagaosa, Ph.D., research assistant

Publication List (year-by-year)

Original Articles (partial list)

International Meetings and Functions (partial list)

Research:: Role for Phagocytosis in Maintenance of Tissue Homeostasis

<Background>

Phagocytosis is a biological reaction where certain types of cells engulf and digest other cells.  Target cells in phagocytosis are either altered self or microbes.  The former cells include obstacles to morphogenesis, aged or spent cells, and cells that have become harmful.  The latter targets are bacteria, fungi, protozoa, and viruses that have invaded our body.  Cells in charge of phagocytosis named “phagocytes” are either circulating our body or present in particular organs.

Phagocytes selectively recognize and engulf target cells, and this cell-cell recognition is presumably achieved through specific binding of cell surface molecules.  The structure of cell surface is apparently different between bacteria and phagocytes, but this is not the case for altered self and phagocytes.  To circumvent this problem, altered self is induced to undergo apoptosis, and a structure that does not exist in normal cells emerges at cell surface.  This structure, called a “phagocytosis marker”, is recognized by a receptor of phagocytes leading to the engulfment of apoptotic cells.

Altered self and invading microbes appear in the body throughout our life.  Such cells are required to be rapidly and selectively eliminated by phagocytosis for tissue homeostasis to be maintained.  Our laboratory is tackling this important biological event with particular aims shown below.

<Projects>

1. Mechanism of Phagocytosis of Microbes and Microbe-Infected Cells to Prevent Infectious Diseases

1-1) Recognition of bacteria by Drosophila phagocytes (hemocytes)

1-2) TLR-mediated regulation of phagocytic elimination of bacteria by mammalian macrophages

1-3) Phagocytosis of influenza virus-infected cells by mammalian phagocytes (macrophages and neutrophils)

2. Mechanism of Phagocytosis of Unwanted Cells for Morphogenesis and Tissue Functions

2-1) Recognition of apoptotic cells by Drosophila phagocytes (hemocytes, glial cells)

2-2) Phagocytosis of PS-exposing cells by mammalian macrophages

2-3) Search for novel phagocytosis markers in mammalian, Drosophila, or C. elegans dying cells

3. Mechanism of Phagocytosis of Unwanted Cells for Regulation of Gamete Production

3-1) Phagocytosis of apoptotic spermatogenic cells by testicular Sertoli cells and its role for spermatogenesis

<Recent publications>

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 (published online on October 21, 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)

Hashimoto, Y., Tabuchi, Y., Sakurai, K., Kutsuna, M., Kurokawa, K., Awasaki, T., Sekimizu, K., Nakanishi, Y., and Shiratsuchi, A. (2009) Identification of lipoteichoic acid as a ligand for Draper in the phagocytosis of Stapylococcus aureus by Drosophila hemocytes. J. Immunol., 183, 7451-7460.

Watanabe, I., Ichiki, M., Shiratsuchi, A. and Nakanishi, Y. (2007). Tlr2-mediated survival of Staphylococcus aureus in macrophages: a novel bacterial strategy against host innate immunity., J. Immunol., 178, 4917-4925. Picked up in the “IN THIS ISSUE”

Hashimoto, Y., Moki, T., Takizawa, T., Shiratsuchi, A. and Nakanishi, Y. (2007). Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice., J. Immunol., 178, 2448-2457. Selected by “Faculty of 1000 Biology, Immunology Section”

Nagaosa, K., Kishimoto, A., Kizu, R., Nakagawa, A. Shiratsuchi, A. and Nakanishi, Y. (2007). Perturbation of spermatogenesis by androgen antagonists directly injected into seminiferous tubules of live mice., Reproduction, 133, 21-27.

by Akiko Shiratsuchi

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