1993 Fiscal Year Final Research Report Summary
Study on the growth, differentiation and function of lung mast cells
| Project/Area Number |
04670458
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
TANNO Yasuo Tohoku University School of Medicine Hospital, Lecturer, 医学部・附属病院, 講師 (20133944)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAUCHI Kohei Tohoku University School of Medicine Hospital, Assistant, 医学部・附属病院, 助手 (20200579)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Mast cell / Basophil / Histamine / Histidine decarboxylase / Tumor necrosis factor / Lung tissue / GATA sequence / Saiboku-to |
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| Research Abstract |
1. We examined TNF production in human lung fragments after IgE receptor triggering at mRNA and protein levels. Cytotoxic activity against L929 cells appeared in the culture supernatant of lung fragments 2 h after IgE receptor triggering and increased for up to 4 h. This cytotoxic activity was completely neutralized by anti-humaan TNF antibody. Northern blot analysis demonstrated that 1.8-kb TNF mRNA transcripts in sensitized lung fragments were expressed as early as 1 h after IgE receptor triggering and continued up to 4 h. Immunohistochemical analysis revealed TNF localization in tissue mast cells, alveolar macrophages, tissue macrophages, and bronchial epithelial cells. Double staining with anti-TNF antibody and alcian blue clearly identified that lung mast cells are one of the TNF-positive cell types in the pulmonary lissue.
2. We have already demonstrated that saiboku-to(Tj-96) has a suppressive effect on the late asthmatic response (LAR) and infiltration of inflammatory cells incl
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uding eosinophils and mast cells into the allergic sites in guinea pigs. In this experiment we examined the effect of this remedy on the expression of TNF-a in a guinea pig asthmatic model. TJ-96 was administered 500 mg/kg/day for 14 days before the challenge using a gastric tube. The control group was given the same volume of water. The immunohistochemistry revealed that TNF-a was strongly expressed in macrophage-like cells, bronchial epithelial cells and alcian-blue positive cells in the lung tissues from asthmatic guinea pigs with LAR, while the expression of this cytokine apeared to be reduced in the TJ-96 treatment group in which LAR was suppressed.
3. Two species of L-histidine decarboxylase(HDC) mRNA were found in the KU-812-F basophilic cell line, but only the 2.4 kb one encodes the functional HDC.The 3.4 kb one encodes a truncated HDC protein, and is also found in human leukemia-derived cell lines HEL and KCL-22. To clarify the mechanisms which regulate transcription of the HDC gene and generate the two species of mRNA, we have isolated genomic DNA clones coding for the HDC from human genomic libraries. Structural analysis of the isolated clones revealed that the human HDC gene is composed of 12 exons spanning approximately 24 kb. Genomic DNA blot analysis suggested that HDC is encoded by a single copy gene. The structural analysis also demonstrated that the heterogeneity of the HDC mRNA is caused by an insertion of the seventh intron sequence and alternative use of the splicing acceptor site at the 12th exon. The transcription start site of the HDC gene, and the nucleotide sequences of the promoter and first exon regions were determined. We found a TATA-like sequence, a GC-box, four CACC-boxes, four GATA consensus sequences, and six LBP-1 binding motifs in the promoter region of the HDC gene. Less
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[Publications] K.Yatsunami, H.Ohtsu, M.Tsuchikawa, T.Higuchi, K.Ishibashi, A.Shida, Y.Shima, S.Nakagawa, K.Yamauchi, M.Yamamoto, N.Hayashi, T.Watanabe, A.Ichikawa: "Structure of the L-histidine decarboxylase gene" Journal of Biological Chemistry. 269. 1554-1559 (1994)
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