Kanji Sakurai

Osaka Medical and Pharmaceutical University

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Hiroshi Takenaka

Okayama University

Takahiro Kubota

Osaka University

Ryotaro Yoshida

Hoshi University

Junko Tashiro‐Yamaji

Osaka Medical and Pharmaceutical University

Koutetsu Lee

Osaka Medical and Pharmaceutical University

Yukio Yoneda

Setsunan University

Masashi Okada

Yamagata University

Masako Miyoshi‐Higashino

Osaka Medical and Pharmaceutical University

Ryo Kawata

Osaka University of Pharmaceutical Sciences

Junko Tashiro

Osaka Medical and Pharmaceutical University

Cooperative Institutions

Osaka Medical and Pharmaceutical University

Osaka University of Pharmaceutical Sciences

Czech Academy of Sciences, Institute of Physiology

Okayama University

Osaka University

Osaka City University

Kyoto University

National Institute of Advanced Industrial Science and Technology

Hiroshima University

University of California, Los Angeles

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Essential Role of Monocytes in theIn VitroProduction of IL-4 and Nonspecific IgE Antibody by Peripheral Blood Lymphocytes from Mice Sensitized s.c. Once with Cedar Pollen

Journal of Interferon & Cytokine Research (2007)

Yumiko Yamamoto Junko Tashiro‐Yamaji Kanji Sakurai Masako Miyoshi‐Higashino Hayahito Nomi

To explore which cytokine or cell is essential for the production of antibodies (Abs) of the IgE class in allergic diseases, we injected cedar pollen into wild-type, interferon-γ−/− (IFN-γ−/−), or interleukin-4−/− (IL-4−/−) BALB/c mice through four (i.n., i.p., s.c., and i.v.) different routes without adjuvant. Wild-type or IFN-γ−/−, but not IL-4−/−, mice sensitized once or twice showed a significant increase in total IgE Ab in their serum, revealing the essential role of IL-4 in the production of total IgE Ab. We separated peripheral blood mononuclear cells (PBMCs) from untreated or sensitized mice into monocyte-rich, lymphocyte-rich, and granulocyte-rich populations by Percoll density-gradient centrifugation or into specific antigen cells by flow cytometry, cultured the cells in various combinations, and examined the levels of cytokines and IgE Ab released into the medium. The PBMCs from mice sensitized s.c. once, but not those from untreated animals, produced significant amounts of IL-4 and total IgE Ab, whereas the lymphocyte-rich population alone did not. Unexpectedly, IL-4 and IgE Ab production was restored by the addition of Mac-1+ cells in the monocyte-rich fraction to the lymphocyte-rich fraction. These results indicate the essential role of monocytes in the production of IL-4 and total IgE Ab by lymphocytes during the initial stage of sensitization.

Monocyte

10.1089/jir.2007.0061

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Citations (7)

Essential role of macrophages in the initiation of allergic rhinitis in mice sensitized intranasally once with cedar pollen: regulation of class switching of immunoglobulin in B cells by controlling interleukin‐4 production in T cells of submandibular lymph nodes

Microbiology and Immunology (2012)

Masayo Hirano Hiromi Ogita‐Nakanishi Wakako Miyachi Natsuki Hannya Yumiko Yamamoto‐Kimoto

The production of allergen-specific IgE antibodies (Abs) in allergen-sensitized patients or animals has a mutual relationship with the immunologic response leading to allergic rhinitis. We recently reported that, after an intranasal injection of cedar pollen into mice, an interleukin-4 (IL-4)-dependent increase in serum nonspecific IgE Abs was a prerequisite for the production of serum allergen-specific IgE Abs. Here, we explored which lymphoid organs were responsive to the intranasally injected allergen and how IL-4 and IgE Abs were produced in the lymphocytes. Time-dependent changes in the total cell numbers and in in vitro IgE Ab production in various lymphoid organs revealed that the submandibular lymph nodes were the main responsible organ. After treatment with allergen (for IgE production) or allergen and complete Freund's adjuvant (for IgG production), we separated submandibular lymph node cells into macrophage-, lymphocyte-, and granulocyte-rich populations by discontinuous Percoll density-gradient centrifugation. Unexpectedly, bulk cells, but not the lymphocyte- or macrophage-rich populations, produced significant amounts of IL-4, IgE, and IgG; whereas production was restored by addition of Mac-1(+) cells from the macrophage-rich to the lymphocyte-rich fraction. Furthermore, a combination of the lymphocyte-rich population (for IgG [or IgE]) production) and the macrophage-rich population (for IgE [or IgG]) production) produced a large amount of IgE (or IgG). These results indicate that, in the initiation of allergic rhinitis, macrophages in the submandibular lymph nodes are essential not only for IL-4 or immunoglobulin production, but also for class switching of immunoglobulin in lymphocytes.

10.1111/j.1348-0421.2012.00449.x

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Differential Susceptibility of Cells Expressing Allogeneic MHC or Viral Antigen to Killing by Antigen-Specific CTL

Microbiology and Immunology (2004)

Koutetsu Lee Hiroshi Takenaka Yukio Yoneda Toshiyuki Goto Kouichi Sano

CD8(+) cytotoxic T lymphocytes (CTLs) generated by immunization with allogeneic cells or viral infection are able to lyse allogeneic or virally infected in vitro cells (e.g., lymphoma and mastocytoma). In contrast, it is reported that CD8(+) T cells are not essential for allograft rejection (e.g., heart and skin), and that clearance of influenza or the Sendai virus from virus-infected respiratory epithelium is normal or only slightly delayed after a primary viral challenge of CD8-knockout mice. To address this controversy, we generated H-2(d)-specific CD8(+) CTLs by a mixed lymphocyte culture and examined the susceptibility of a panel of H-2(d) cells to CTL lysis. KLN205 squamous cell carcinoma, Meth A fibrosarcoma, and BALB/c skin components were found to be resistant to CTL-mediated lysis. This resistance did not appear to be related to a reduced expression of MHC class I molecules, and all these cells could block the recognition of H-2(d) targets by CTLs in cold target inhibition assays. We extended our observation by persistently infecting the same panel of cell lines with defective-interfering Sendai virus particles. The Meth A and KLN205 lines infected with a variant Sendai virus were resistant to lysis by Sendai virus-specific CTLs. The Sendai virus-infected Meth A and KLN205 lines were able to block the lysis of Sendai virus-infected targets by CTLs in cold target inhibition assays. Taken together, these results suggest that not all in vivo tissues may be sensitive to CTL lysis.

Sendai virus

CTL*

10.1111/j.1348-0421.2004.tb03483.x

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A Clinical Study of Ultrasonography for Lymph Node Metastases in head and Neck Cancer

Nippon Jibiinkoka Gakkai Kaiho (2003)

Ibuki Hayashi Ryo Kawata Koutetsu Lee Kanji Sakurai Yuuichirou Tsuji

Ultrasonography (US) is very useful in evaluating cervical lymph node swelling in head and neck cancers. We studied problems with US in evaluating lymph nodes. Cervical lymph nodes were removed by radical neck dissection or modified radical neck dissection from 79 patients with squamous cell carcinoma in the head and neck. We studied the correlation between preoperative US findings and the histopathological features. Preoperative lymph nodes were measured three-dimensionally. We diagnosed lymph nodes as metastases when they meet two criteria: One is the shortest diameter exceeding 7 mm in level I and II and 6 mm in level III, IV and V. The other is shortest to longest diameter ratio exceeding 0.5. A total of 2004 lymph nodes were removed by neck dissection, and 199 lymph nodes were diagnosed histopathologically as metastases. Of the 199 metastatic lymph nodes, 93 (46%) were diagnosed as metastases by preoperative US findings and 33 (17%) were false negative. Thirty-six cases were diagnosed preoperatively as N0 by US findings, but 15 of these were pN(+) histopathologically. In the 15 cases, 21 lymph nodes were metastases. Of the 21 metastatic lymph nodes, 10 nodes were not detected by US. Thirty-one cases were diagnosed preoperatively as N1 by US findings, but 20 of these were pN2b histopathologically. In the 20 cases, 66 lymph nodes were metastases. Of the 66 metastatic lymph nodes, 46 were not diagnosed as metastases. They often located distant level from the lymph node diagnosed correctly as a metastasis. US is very useful in evaluating cervical lymph node metastasis, but it has the limitations indicated above. If 1 metastatic lymph node is detected by US, there will be multiple metastatic lymph nodes and sometimes they are distant from the original level. Radical neck dissection should be done for positive lymph nodes detected by US findings. If a lymph node is not clearly a metastasis, fine-needle aspiration cytology (FNA) should be done, because it provides more accurate diagnosis for metastatic lymph nodes.

Neck dissection

Cervical lymph nodes

10.3950/jibiinkoka.106.499

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Citations (4)

Cellular Origin of IFN-γEssential for Hair Cycle in Normal Skin

Journal of Interferon & Cytokine Research (2003)

Yukio Yoneda Ryuichiro Hirota Junko Tashiro Masashi Okada Kanji Sakurai

Hair growth abnormalities in mice usually are accompanied by histologic abnormalities as well. Recently, however, we reported a mouse model in which an arrest of the hair cycle and diffuse shedding of the hair without pathologic features induced alopecia in interferon-gamma(-/-) (IFN-gamma(-/-)) C57BL/6 (B6) mice. Here, we explored the cellular origin of IFN-gamma. When bone marrow from IFN-gamma(-/-) B6 mice was transplanted into lethally irradiated IFN-gamma(+/+) B6 mice, the level of IFN-gamma mRNA expression in the skin or peripheral blood mononuclear cells (PBMCs) of recipient mouse was markedly reduced, suggesting that IFN-gamma is normally produced by bone marrow-derived cells. Although severe combined immunodeficiency (SCID) mice lack mature T cells and B cells, IFN-gamma-dependent hair regrowth was induced in SCID mice by depilation, which caused alopecia in IFN-gamma(-/-) B6 mice. Consistently, IFN-gamma mRNA expression in the skin or PBMC from SCID mice was comparable to that from their genetic counterpart (BALB/c mice), suggesting IFN-gamma production by non-T cells. RT-PCR analyses after separation of PBMC from SCID mice into eight fractions by a cell sorter revealed that Mac-1(+) cells were the major origin of IFN-gamma.

Hair cycle

Interferon γ

10.1089/107999003766628142

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Citations (7)

IgE Production after Four Routes of Injections of Japanese Cedar Pollen Allergen without Adjuvant: Crucial Role of Resident Cells at Intraperitoneal or Intranasal Injection Site in the Production of Specific IgE toward the Allergen

Microbiology and Immunology (2005)

Kanji Sakurai Hiroshi Takenaka Yukio Yoneda Junko Tashiro‐Yamaji Yumiko Yamamoto

Abstract The production of specific IgE antibodies directed toward cedar pollen correlates well with the onset of allergic rhinitis; but the mechanisms of allergen recognition as nonself and Ig class switch to IgE by the immune system are still not fully understood. In the present study, we injected cedar pollen into mice through 4 different routes (intranasal (i.n.), intraperitoneal (i.p.), intravenous (i.v.), and subcutaneous (s.c.)) without adjuvant 1 to 3 times, and determined time‐dependent changes in the total and specific serum IgE levels compared with those in the serum levels of other isotype Igs. After an i.p. or i.n. injection of allergen into the mice, they produced a 1.5‐ to 1.7‐fold increase in total IgE, but none in IgG, IgM, or IgA antibodies in their serum, whereas an i.v. or s.c. injection of allergen was inactive as an inducer of total IgE antibodies. Upon a 2nd (s.c.) injection of the allergen into the i.p. or i.n. sensitized mice, a large amount of allergen‐specific IgE antibodies was found in the serum. In the case of i.v. or s.c. sensitized mice, however, they produced total, but not specific, IgE antibodies; and a 3rd (s.c.) injection of the allergen resulted in a large amount of specific IgE antibodies in the serum. These results imply that resident cells at the i.p. or i.n. injection site may play a crucial role in the efficient production of total and specific IgE antibodies toward the allergen.

Isotype

Intraperitoneal injection

Subcutaneous injection

10.1111/j.1348-0421.2005.tb03747.x

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Citations (7)

IL‐4‐dependent induction of IgE⁺ basophils in peripheral blood and IgE⁺ B cells in spleen as respective indicators of allergen sensitization and a precursor of cells secreting allergen‐specific IgE antibody

Microbiology and Immunology (2009)

Masako Miyoshi‐Higashino Masayo Hirano Hiromi Ogita‐Nakanishi Yumiko Yamamoto‐Kimoto Kanji Sakurai

ABSTRACT It was recently reported by us that either primary i.n. or i.p. injection of cedar pollen extract into BALB/c mice, or a second s.c. injection of the allergen into i.v. or s.c. sensitized mice, causes an IL‐4‐dependent increase in total IgE serum antibody to produce allergen‐specific IgE antibody upon further s.c. sensitization. To determine the biology of total IgE antibody, in the present study IgE + cells in peripheral blood or lymphoid tissues of allergen‐sensitized BALB/c mice have been characterized. In peripheral blood, mice sensitized one to three times with the allergen produced a 2.5‐ to 4‐fold increase in the number of IgE + cells, with a time‐course similar to that of the concentration of total IgE antibody in serum. These IgE + cells were basophils. On the other hand, the number of IgE + cells in the lymphoid tissues did not change significantly after an i.n., i.p., i.v. or s.c. injection of allergen into the mice, whereas a second s.c. injection of the allergen into the i.v.‐, but not into the i.n.‐, i.p.‐ or s.c.‐, sensitized mice induced a small number of IgE + /IgM + /B220 + B cells in the spleen. In contrast, IgE + cells were not seen in the blood or spleen of IL‐4 ‐/‐ mice after sensitization with the allergen. These results suggest that IgE + basophils in the peripheral blood, and IgE + B cells in the spleen, might be IL‐4‐dependently induced as an indicator of sensitization with allergen, and a precursor of cells secreting allergen‐specific IgE antibody, respectively.

10.1111/j.1348-0421.2008.00088.x

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A Device for Resection of Epiglottal Cysts.

Practica Oto-Rhino-Laryngologica (2000)

Masashi Imanaka Kanji Sakurai Toshihide Atago Atushi Sakakura Hiroshi Takenaka

Epiglottal cysts in the larynx are not rare, but a standard resection method has not yet been established. We reported a new device and technique for resection of epiglottal cysts. According to usual laryngomicrosurgery, we approached the cyst by means of Karl Storz's direct laryngoscope and used scissors and forceps for laryngomicrosurgery. We treated the cyst wall with the scissors and forceps while they were electrified by an electrotome. Epiglottal cysts were removed easily, rapidly, and completely, and the hemostasis was easily obtained.This “electrolaryngomicrosurgery” is an idea resembling that of Columbus' egg; however, it makes resection of epiglottal cysts easy and certain.

10.5631/jibirin.93.501

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