2000 Fiscal Year Final Research Report Summary
Induction of Cell Death upon Infection with Shigella flexneri
| Project/Area Number |
11670139
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IMAJOH-OHMI Shinobu Medical Science, Basic Medical Sciences, The University of Tokyo Associate Professor, 医科学研究所, 助教授 (20160046)
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| Co-Investigator(Kenkyū-buntansha) |
NONAKA Takashi Medical Science, Basic Medical Sciences, JSPS Fellow, 医科学研究所, 日本学術振興会特別研究員
SASAKAWA Chihiro Medical Science, Microbiology and Immunology, The University of Tokyo Professor, 医科学研究所, 教授 (70114494)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Shigella / Bacterial infection / Apoptosis / Cell death / Ipa protein / Cell differentiation / macrophage / caspase |
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| Research Abstract |
Upon invasion into tissues bacterial phathogens are phagocytosed by resident macrophages to be killed and digested. Some bacteria can escape into the cytosol and induce cell death of the host cell.
Shigella flexneri is also reported to induce apoptosis in murine macrophages where a bacterial invasion plasmid antigen B (IpaB) activates a cellular protease triggering apoptotic cell death. However, other investigators observed necrotic cell death in Shigella-infected human macrophages derived from peripheral monocytes. Cell death of macrophages caused by bacterial invasion remains to be characterized on the basis of molecular interaction.
We employed here a human monoblastic cell line U937 that is poteittially differentiated into cells resembling mature monocytes in the peripheral blood. Cultured with IFNgamma or RA, U937 cells become superoxide anion-producible. When S.flexneri was introduced into thus differentiated cells, cell death occurred regardless of differentiation stateas as judge
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d by the dye exclusion viability test. Cell death was also observed in undifferentiated U937 cells, but was strongly promoted in RA-differentiated cells. On the other hand, an avirulent mutant strain deficient in Ipa proteins did not induce cell death, probably because bacteria could not enter the cell. These results clearly indicate that bacterial invasion induces cell death in monocyte-like U937 cells. However, undifferentiated and RA-differentiated U937 cells died exhibiting cytoplasmic swelling but not nuclear condensation and fragmentation, suggesting that these cells underwent necrosis. Surprisingly, IFNgamma-differentiated U937 cells showed morphological features typical of apoptosis, though these cells were as sensitive as undifferentiated U937 to virulent Shigella. These observations were confirmed by DNA fragmentation assay on an agarose gel where chromosomal DNA from IFNgamma-treated cells was electrophoresed in a ladder-like manner upon Shigella infection but that from U937 cells of different differentiation state was not. Furthermore, cleavage of PARP was seen only when IFNgamma-differentiated cells were infected with pathgenic Shigella. These findings suggest that vilulent Shigella induces distinct types of cell death in U937 cells depending on their differentiation state. Less
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[Publications] Fujikawa, H., Tani, E., Yamaura, I., Ozaki, I., Miyaji, K., Sato, M., Takahashi, K., and Imajoh-Ohmi, S.: "Activation of protein kinases in canine basilar artery in vasospasm."J Cereb Blood Flow Metab. 19 (1). 44-52 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Horie, R., Gattei, V., Ito, K., Imajoh-Ohmi, S., Tange, T., Miyauchi, J., Pinto, A., Degan, M., De luliis, A., Tassan Mazzocco, F., Rossi, F.M., Higashihara, M., and Watanabe, T.: "Frequent Expression of the Variant CD30 in Human Malignant Myeloid and Lymphoid Neoplasms."Am J Pathol. 155 (6). 2029-2041 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kawakami, T., Kaneko, A., Okada, N., Imajoh-Ohmi, S., Nonaka, T., Matsui, H., Kawahara, K., and Danbara, H.: "TTG as the initiation codon of Salmonella slyA, a gene required for survival within macrophages."Microbiol Immunol. 43 (4). 351-357 (1999)
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[Publications] Shiroki, K., Isoyama, T., Kuge, S., Ishii, T., Imajoh-Ohmi, S., Hata, S., Suzuki, K., Takasaki, Y., and Nomoto, A.: "Intracellular redistribution of truncated La protein produced by poliovirus 3Cpro-mediated cleavage."J Virol. 73 (3). 2193-2200 (1999)
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[Publications] Inoue, Y., Itou, T., Jimbo, T., Sakai, T., Ueda, K., Imajoh-Ohmi, S., and Iida, T.: "Molecular cloning and identification of bottle-nosed dolphin flavocytochrome b gp91 (phox) and p22 (phox) subunits."Vet Immunol Immunopathol. 76 (1-2). 137-150 (2000)
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[Publications] Kishimoto, S., Sakon, M., Umeshita, K., Miyoshi, H., Taniguchi, K., Meng, W., Nagano, H., Dono, K., Ariyosi, H., Nakamori, S., Kawasaki, T., Gotoh, M., Monden, M., and Imajoh-Ohmi, S.: "The inhibitory effect of prostaglandin E1 on oxidative stress-induced hepatocyte injury evaluated by calpain-mu activation."Transplantation. 69 (11). 2314-2319 (2000)
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[Publications] Tamano, K., Aizawa, S.I., Katayama, E., Nonaka, T., Imajoh-Ohmi, S., Kuwae, A., Nagai, S., and Sasakawa, C.: "Supramolecular structure of the Shigella type III secretion machinery : the needle part is changeable in length and essential for delivery of effectors."Embo J. 19 (15). 3876-3887 (2000)
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[Publications] Yamada, M., Ariga, T., Kawamura, N., Ohtsu, M., Imajoh-Ohmi, S., Ohshika, E., Tatsuzawa, O., Kobayashi, K., and Sakiyama, Y.: "Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease : detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients."Br J Haematol. 108 (3). 511-517 (2000)
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