論文 - 丸山 治彦
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Molecular cloning of mouse intestinal trefoil factor and its expression during goblet cell changes
Tomita M., Itoh H., Ishikawa N., Higa A., Ide H., Murakumo Y., Maruyama H., Koga Y., Nawa Y.
Biochemical Journal 311 ( 1 ) 293 - 297 1995年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical Journal
A cDNA encoding mouse intestinal trefoil factor (mITF) was successfully cloned and sequenced from the small intestine of C57BL/6 mouse by using the combination of reverse transcription-PCR and rapid amplification of cDNA ends methods. The gene was, similar to rat and human ITFs, mainly expressed in the small and large intestine. The mITF expression was up-regulated during the recovery phase after depletion of goblet cells in acetic acid-induced colitis. On the other hand, the expression in the jejunum was not altered, while goblet cell hyperplasia was induced by Nippostrongylus brasiliensis infection. These results suggest that the mITF expression did not simply correlate with the number of goblet cells. The mITF may play an important role in the maintenance and repair of mucosal function of the rectum. Additionally, the mITF in the jejunum may play a role in alteration of the physicochemical nature of goblet cell mucins, thereby affecting the establishment of intestinal helminths.
DOI： 10.1042/bj3110293
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Herlyn D., Harris D., Zaloudik J., Sperlagh M., Maruyama H., Jacob L., Kieny M., Scheck S., Somasundaram R., Hart E., Ertl H., Mastrangelo M.
Journal of Immunotherapy 15 ( 4 ) 303 - 311 1994年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Immunotherapy
Monoclonal anti-idiotypic antibody (Ab2) VF2 was derived from rats immunized with anti-colorectal carcinoma (anti-CRC) monoclonal antibody (Abl) CO17–1A. In rabbits the Ab2 induced anti anti-idiotypic antibodies (Ab3) that shared idiotopes with the Abl, bound to the same epitope on CRC cells as Abl, and bound to the isolated CO17–1A antigen. Monoclonal Ab2 VF2 was superior to the previously described polyclonal goat Ab2 against Abl CO17–1A in its capacity to elicit humoral immunity in animals. Ab2 VF2 also induced a specific delayed-type hypersensitivity (DTH) response to challenge with irradiated CO17–1A antigen-positive human CRC cells in mice. Of nine CRC patients immunized with aluminum hydroxide-precipitated Ab2 VF2, six developed antibodies that bound to Ab2, but only three patients developed Ab3 that bound to idiotypic determinants on Ab2. However, the Ab3 did not bind to CO17–1A antigen-positive CRC cells. In contrast, in a previously described trial with polyclonal goat Ab2 to Abl CO17–1A, most of the patients developed anti-CRC antibodies. Four of the nine patients immunized with Ab2 VF2 developed DTH responses to intradermal challenge with the Ab2, and in one patient DTH was both Ab2− and antigen-specific. Peripheral blood mononu-clear cells of the four DTH-reactive patients did not proliferate in response to in vitro stimulation with either Ab2 or antigen. These studies demonstrate that the immunomodulatory activity of monoclonal Ab2 VF2 in animals is only in part predictive of its activity in patients. © 1984 Journal of Immunotherapy. All rights reserved.
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Polyclonal antiidiotypic antibodies mimicking gp 120 of HIV-1
Sperlagh M., Hoxie J., Maruyama H., Stefano K., Gonzales-Scarano F., Prewett M., Liang S., Matsushita S., Herlyn D.
Viral Immunology 7 ( 2 ) 61 - 69 1994年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Viral Immunology
Rabbit antiidiotypic antibodies (Ab2) were produced against anti-HIV-1 antibody 0.5β (Ab1), which binds to gp120 of HIV-1 and shows virus-neutralizing activity. The Ab2 bound specifically to the Ab1 and their binding to Ab2 was inhibited by a recombinant fragment of gp120 (PB1) or a peptide (residues 301-324 of gp120), both expressing the Ab1-defined epitope. The Ab2 induced in rats antiantiidiotypic antibodies (Ab3) that were Ab1-like in their binding reactivities to PB1, native gp120 or peptide and shared idiotopes with the Ab1. However, the Ab2 did not induce virus-neutralizing Ab3, probably a reflection of the low avidity of the Ab3 as compared to the Ab1.
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Sperlagh M., Stefano K., Gonzalez-Scarano F., Liang S., Hoxie J., Maruyama H., Prewett M., Matsushita S., Herlyn D.
AIDS 7 ( 12 ) 1553 - 1559 1993年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：AIDS
Objective: To develop effective, specific and safe anti-idiotypic antibody (Ab2) vaccines against HIV-1. Design: Murine monoclonal Ab2 were generated against anti-HIV-1 antibody 0.5β (Ab1), which binds to gp120, neutralizes HIV-1 and inhibits virus-induced syncytia formation. Methods: Mice were immunized with Ab1, and Ab2 were produced from immunized mice by the hybridoma technique. The Ab2 were characterized in vitro, injected into rabbits, and the anti-anti-idiotypes (Ab3) induced in the rabbits were analyzed for binding and antiviral reactivities by enzyme-linked immunosorbent assay, p24gag release and syncytia formation assays. Results: Seven Ab2 bound to the antigen-combining site of Ab1, one of which (UD7) induced Ab3 in rabbits that were Ab1-like in their binding reactivities to PB1 (recombinant gp120 fragment) or peptides of gp120, and shared idiotypes with the Ab1. Crude Ab3-containing sera specifically and effectively neutralized the virus. Conclusion: Monoclonal Ab2 UD7 has potential as a vaccine against HIV-1.
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Makoto O., Shiroh F., Kouki K., Yoichiro H., Haruhiko M., Hiromi H., Yukifumi N.
Molecular Immunology 30 ( 14 ) 1315 - 1320 1993年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Molecular Immunology
To compare the molecular structure of a parasite-derived neutrophil chemotactic factor (NCF) with host-derived NCFs or other NCFs, molecular cloning of cDNA encoding NCF derived from Dirofilaria immitis adult worm (DiNCF) was performed. A D. immitis cDNA library was screened with an antibody to DiNCF, and one DiNCF cDNA clone (pD-4) was isolated. A fusion protein of pD-4 and gene 10 protein showed significant neutrophil chemotactic activity whereas gene 10 protein itself showed marginal neutrophil chemotactic activity. The total nucleotide sequence analysis revealed that pD-4 was 994 bp long with a 432 bp open leading frame encoding a 143 residue protein. The NH 2 -terminal amino acid sequence of the natural DiNCF and the deduced amino acid sequence from the cDNA showed that the mature functional protein was comprised of 112 amino acids. Although the deduced amino acid sequence of this protein did not show overall homology to host-derived NCFs or other known proteins, it contained a similar sequence (Met-Phe-Lys) to the known chemotactic peptides. The possibility of the functional epitope of DiNCF is discussed. © 1993.
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Levi M., Sällberg M., Rudén U., Herlyn D., Maruyama H., Wigzell H., Marks J., Wahren B.
Proceedings of the National Academy of Sciences of the United States of America 90 ( 10 ) 4374 - 4378 1993年5月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Proceedings of the National Academy of Sciences of the United States of America
A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I - GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons.
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Molecular cloning of murine monoclonal anti-idiotypic Fab
Kasai Y., Herlyn D., Sperlagh M., Maruyama H., Matsushita S., Linnenbach A.
Journal of Immunological Methods 155 ( 1 ) 77 - 89 1992年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Immunological Methods
Anti-idiotypic antibodies (Ab2) binding to idiotopes on antibodies with various antigen binding specificities (Ab1) are potential regulators of immunity in a variety of diseases, such as autoimmunity, cancer, and viral, bacterial, or parasitic infections. Furthermore, Ab2 are useful probes for the characterization of receptor/ligand interactions. Thus far, Ab2 production has been limited to the isolation of polyclonal Ab2 from immune sera or monoclonal Ab2 from hybridoma supernatants. However, both approaches have produced a limited number of Ab2. As an alternative approach, we demonstrate here the production of Ab2-Fab by using repertoire cloning. Using HIV-1 as a model system, the Ab2-Fab were generated from the spleens of mice immunized with the virus-neutralizing and syncytia-inhibiting anti-HIV-1 monoclonal antibody 0.5β. A bacteriophage γ vector system was used to express a combinatorial library in Escherichia coli. Iodinated 0.5β was used to identify 17 Ab2-Fab clones. DNA sequence analysis of five clones revealed three similar κ and Fd combinations. The Ab2-Fab bound with high affinity (3.5-6.5 × 109 liters/mol) specifically to the Ab1 and not to isotype-matched antibodies with unrelated specificities. The three Ab2-Fab probably bind to the same idiotope on the Ab1 as demonstrated in cross-competition binding studies. The Ab2-Fab inhibited binding of the Ab1 to antigen, and therefore, may functionally mimic the epitope defined by the Ab1. Repertoire cloning of Ab2-Fab may facilitate the generation of Ab2 that have potential as modulators of immune responses against various antigens. © 1992.
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Hepatic eosinophilopoiesis from multipotent hemopoietic stem cells in Toxocara canis-infected mice
Maruyama H., Higa A., Asami M., Owhashi M., Nawa Y.
Experimental Hematology 19 ( 2 ) 77 - 80 1991年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Experimental Hematology
Extramedullary hemopoiesis, recognized as hemopoietic foci, increased in the livers of Toxocara canis-infected mice. At the peak of the response (day-13 after infection), the majority of hepatic hemopoietic foci were of the eosinophil lineage. Hepatic nonparenchymal cells prepared from T. canis-infected mice on day 13 contained large numbers of hemopoietic stem cells, more than half of which were cycling. When W/W(v) mice, which are genetically deficient in multipotent hemopoietic stem cells, were infected with T. canis, hepatic hemopoietic foci were rare throughout the course of infection. This impaired response of W/W(v) mice was restored by bone marrow grafting from normal +/+ littermates. These results indicate that, in response to the increased demand, eosinophils are generated in the liver by the differentiation from multipotent stem cells, not only from the committed precursors.
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Owhashi M., Horii Y., Ikeda T., Maruyama H., Abe T., Nawa Y.
International Archives of Allergy and Immunology 92 ( 1 ) 64 - 68 1990年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Archives of Allergy and Immunology
The role of mast-cell-derived eosinophil chemotactic factor A (ECF-A) on eosinophil-rich peri-ovular granuloma formation was examined by using mast-cell-deficient WBB6F1-W/W mice infected with Schistosoma japonicum. The average size of granulomas formed around newly deposited eggs in the liver of W/W<sup>v</sup> mice was significantly smaller than that observed in control +/+ mice. The number of adult worms recovered or specific IgE titers were comparable between W/W<sup>v</sup> and +/+ mice. In contrast, immediate-type hypersensitivity response to specific antigen and dialyzable low-molecular weight ECF in the serum was detectable only in infected +/+ mice. When naive bone marrow eosinophils were incubated with the dialyzable fraction of infected +/+ mice sera, chemotactic reactivity of eosinophils to ECF derived from S. japonicum eggs was significantly enhanced, although that to synthetic ECF-A was depressed. Similar effects were observed when naive eosinophils were treated with synthetic ECF-A. The dialyzable fraction of infected W/Wv mice sera had no such modulating effect on the chemotactic reactivity of eosinophils. These results suggest that an immediate-type hypersensitivity reaction is important in the formation of eosinophilic granulomas around S. japonicum eggs, mainly through the modulating effect of mast-cell-derived ECF-A on the chemotactic reactivity of eosinophils. © 1990 S. Karger AG, Basel.
DOI： 10.1159/000235226
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NAWA Y., ABE T., IMAI J., MARUYAMA H.
Parasite Immunology 10 ( 2 ) 117 - 126 1988年3月
担当区分：最終著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Parasite Immunology
Summary The susceptibility of C57BL/6‐bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak‐Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJbgJ mice was approximately twice as high as that of their littermate bgJ/+ mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+ mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine lo become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+ mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells. Copyright © 1988, Wiley Blackwell. All rights reserved
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Owhashi M., Maruyama H., Nawa Y.
Infection and Immunity 55 ( 9 ) 2042 - 2046 1987年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Infection and Immunity
Granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by splenic lymphocytes obtained from Schistosoma japonicum-infected mice was partially purified by a combination of DEAE anion-exchange chromatography, concanavalin A-Sepharose affinity chromatography, and high-pressure liquid chromatography. When this partially purified GM-CSF was added to the culture of isolated intact granulomas, eosinophil chemotactic factor (ECF) lymphokine production by granulomas was significantly enhanced. The partially purified GM-CSF also enhanced ECF lymphokine production by granuloma T cells cocultured with syngeneic macrophages and specific antigen. The partially purified GM-CSF itself had neither ECF activity nor a synergistic effect with ECF lymphokine. When normal splenic macrophages were preincubated with the partially purified GM-CSF, they potentiated the ECF production by granuloma T cells under the presence of specific antigen. Augmentation of ECF lymphokine production by partially purified GM-CSF was further confirmed by using T-cell clones that were established from granuloma T cells. These results suggest that T-cell-derived GM-CSF primarily activate macrophages so that these activated macrophages can cooperate more effectively with T lymphocytes to produce ECF. Such potentiation of macrophage-T-cell interaction by GM-CSF may be important in the mechanisms of granuloma formation during an acute stage of schistosomiasis.
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Owhashi M., Maruyama H., Nawa Y.
Infection and Immunity 54 ( 3 ) 723 - 727 1986年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Infection and Immunity
Eosinophil chemotactic factor (ECF) was detected in the culture supernatant of isolated intact egg granulomas from the livers of Schistosoma japonicum infected mice. This factor had an apparent molecular weight of 15,000 by high-pressure liquid chromatography with an SW3000 column and bound to concanavalin A-Sepharose 4B. When cells obtained by enzymatic digestion of isolated granulomas were cultured under the presence of soluble egg antigen of S. japonicum or concanavalin A, ECF was also detected in the conditioned medium. The physicochemical nature of the ECF produced by concanavalin A-stimulated granuloma cells was similar to that produced by isolated intact granulomas. The ECF-producing activity of the cells was abolished by pretreatment with anti-Thy-1.2 or anti-Lyt-1.2 monoclonal antibody and complement but not by anti-Lyt-2.2 antibody. Furthermore, nylon wool-passed, T-enriched granuloma cells required collaboration of syngeneic macrophages to produce ECF. These results suggest that Lyt-1-positive T cells in the granuloma could, in collaboration with macrophages, produce ECF and thereby attract eosinophils to this lesion.