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1998 Fiscal Year Final Research Report Summary

Functional coupling of lipid mediator-metabolizing enzymes in mast cell

Research Project

Project/Area Number 09680702
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionShowa University

Principal Investigator

MURAKAMI Makoto  Showa University, School of Pharmaceutical Sciences, Assistant professor, 薬学部, 助教授 (60276607)

Project Period (FY) 1997 – 1998
KeywordsMast cells / Arachidonic acid / PGD_2 / PAF / LTC_4 / Cytokine / IgE / Antigen / Phospholipase A_2
Research Abstract

In the present study, we have examined the functional coupling between various enzymes involved in the metabolism of lipid mediators, such as prostaglandins (PGs) and platelet-activating factor (PAF), using mouse bone marrow-derived mast cells (BMMC), rat mastocytoma RBL, and rat serosal mast cells (CTMC).
1. Arachidonic acid (AA) metabolism
We found that mast cells elicit a biphasic PGD_2-biosynthetic response after stimulation with FcepsilonRI crosslinking in combination with particular cytokines. In the immediate phase, which occurred within several minutes, the AA liberated from membrane phospholipids by the action of cytosolic phospholipase A_2 (cPLA_2) was converted by the constitutive cyclooxygenase (COX) isoform, COX-1, to PGD_2. In the delayed phase, which occurred during 5-10 h after stimulation, the AA released by the constitutive cPLA_2 and inducible secretory PLA_2 (sPLA_2) was presented to inducible COX-2 in marked peference to COX-l, leading to sustained PGD_2 generation. The major sPLA_2 isozymes expressed in mast cells were types IIA and V sPLA_2, which contributed to delayed PGD_2 generation by augmenting COX-2 expression.
2. PAF metabolism
Activated mast cells produced PAF, which reached a peak within a few minutes and declined rapidly thereafter. This rapid inactivation of PAF was mediated by a secretory form of PAF-acetylhydrolase, which was released by exocytosis following mast cell activation. The expression of PAF-acetylhydrolase was upregulated by particular combination of cytokines.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Tada, K.et al.: "Induction of COX-2 by sPLA_2s in NGF-stimulated rat serosal mast cells is facilitated by interaction with fibroblasts and mediated by a mechamism independent of their enzymatic functions." J.Immunol.161. 5008-5015 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Moon, T.C.et al.: "Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial LPS that acts in synergy with c-kit ligand and Fc, Rl crosslinking in cultured mast cells." Cell.Immunol.185. 146-152 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakajima, K.et al.: "Activated mast cells release extracellular type platelet-activating tactor acetylhydrolase that contributes to autocrine inactivation of platelet-activating factor." J.Biol.Chem.272. 19708-19713 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami, M.et al.: "COX-2-dependent delayed PGD_2 generation is initiated by NGF in rat peritoneal mast cells : its augmentation by extracellular type II secretory PLA_2." J.Immunol.159. 439-446 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami, M.et al.: "Detection of secretory phospholipase A_2s related but not identical to type IIA isozyme in cultured mast cells." FEBS Lett.413. 249-254 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ogasawara, T.et al.: "Mouse BMMC undergo exocytosis, prostanoid generation and cytokine expression in response to G protein-activating polybasic compounds after coculture with fibroblasts in the presence of KL." J.Immunol.158. 393-404 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tada, K., Murakami, M., Kambe, T., and Kudo, I.: "Induction of cyclooxygenase-2 by secretory phospholipase A_2s in nerve growth factor-stimulated rat serosal mast cells ins facilitated by interaction with fibroblasts and mediated by a mechamism independent of their enzymatic functions." J.Immunol.161. 5008-5015 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Moon, T.C., Murakami, M., Ashraf, M.M.D., Kudo, I., and Chang, H.W.: "Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial lipopoly-saccharide that acts in synergy with c-kit Ligand and Fce receptor I crosslinking in cultured mast cells." Cell.Immunol.185. 146-152 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, K., Murakami, M., Yanoshita, R., Samejima, Y., Karasawa, K., Setaka, M., Nojima, S., and Kudo, I.: "Activated mast cells release extracellular type platelet-activating factor acetylhydrolase that contributes to autocrine inactivation of platelet-activating factor." J.Biol.Chem.272. 19708-19713 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami, M., Tada, K.Nakajima, K., and Kudo, I.: "Cyclooxygenase-2-dependent delayed prostaglandin D_2 generation is initiated by nerve growth factor in rat peritoneal mast cells : its augmentation by extracellular type II secretory phospholipase A_2." J.Immunol.159. 439-446 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami, M., Tada, K., Shimbara, S., Kambe, T., Sawada, H., and Kudo, I.: "Detection of secretory phospholipase A_2s related but not identical to type IIA isozyme in cultured mast cells." FEBS Lett.413. 249-254 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ogasawara, T., Murakami, M., Suzuki-Nishimura, T., Uchida, M.K., and Kudo, I.: "Mouse bone marrow-derived mast cells undergo exocytosis, prostanoid generation and cytokine expression in response to G protein-activating polybasic compounds after coculture with fibroblasts in the presence of c-kit ligand." J.Immunol.158. 393-404 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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