A Research for the Development of Antiallergic-Drug with using Growing Differentiated Mast Cells in Culture System
| Project/Area Number |
60480461
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
ICHIKAWA Atsushi Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University., 薬学部, 教授 (10025695)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Tetsuya Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Kyoto Univer, 薬学部, 助手 (90111971)
SAITO Terumi Department of Health Chemistry, Faculty of Pharmaceutical Sciences, Kyoto Univer, 薬学部, 助教授 (80025717)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1985: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Mast cells / Allergy / Prostaglandin / Histidine decarboxylase / Histamine / Differentiation / 細胞培養 |
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| Research Abstract |
We obtained the following results with a serious study how to grow the well-differentiated mast cells in vitro culture system. The cultured mast cells are beneficial to develop the mechanism of action of anti-allergic drugs or to judge their effectiveness quickly.
1. Preparation and cultivation of differentiated mast cells: During cultivation in serum-containing medium, well-differentiated peritoneal mast cells gradually lost their histamine-containing granules. However, the disappearance was protected by addition of conditioned medium from, or by co-cultivation with fetal liver cells as a feeder layer cells. Some of grown mast cells have an axon like a single nerve cells. This transformation in shape was accelerated by adding large amount of conditioned medium from fetal cells. IL-3 dependent mast cells (P-3 cells) was also cultivated in the presence of conditioned medium from WHEI cells. Mastocytoma P-815 cells were grown in the presence of butyrate or glucocorticoid. Butyrate stimulated evry differentiation activities (histamine-, serotnin-, heparin-synthesis and granulopoiesis), while glucocorticoid only his-tidine decarboxylase synthesis.
2) Cell activities of cultivated mast cells in the synthesis and the secretion of biological active compounds: DNP-ascaris antiserum and active oligomer of compound 48/80 stimulated the secretion of histamine and various arachidonic metabolites fron cultured mast cells. Also, degranulated mast cells gradually reconstituted their biological amines in granules by cAMP or glucocorticoid.
3) Well-known antiallergic drugs effectively and dose-dependently suppressed the <Ca^(2+)> -dependent secretion mechanism of every types of cultured mast cells. These results show that the cultured mast cells appear to be available in the research and the development of anti-allergic drugs in associaton with the mast cell function.
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Report
(1 results)
Research Products
(11 results)
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[Publications] Dainaka, Junichi., Ichikawa, Atsushi., Koibuchi, Yasushi., Nakagawa, Mihoko & Tomita, Kenkichi.: "Effect of the tridecamer of compound 48/80, A <Ca^(2+)> -dependent histamine releaseer, on phospholipid metabolism during the early stage of histamine release from mast cells." Biochemical Pharmacology. 35. 3739-3744 (1986)
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[Publications] Imanishi, Noriaki., Nakayama, Takahiro, Asano, Mami., Yatsunami, Kimio, Tomita, Kenkichi & Ichidawa, Atsushi.: "Induction of histidine decarboxylase by dexamethasone in mastocytoma P-815 cells." Biochimica Biophysica Acta. in press. (1987)
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