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Inhibition of stem cell factor- and nerve growth factor-induced morphological change by wortmannin in mast cells

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Abstract

Recombinant murine stem cell factor (rmSCF) or recombinant murine nerve growth factor (rmNGF) induced the morphological change of large numbers of rat peritoneal mast cells (RPMC). We investigated the role of phosphatidylinositol 3′-kinase (PI3-kinase) in receptors-mediated morphological change in RPMC. Exposure of RPMC to PI3-kinase inhibitor, wortmannin, before the addition of rmSCF and rmNGF antagonized those factors-induced morphological change. These results suggest that the PI3-kinase is involved in the signal transduction pathway responsible for morphological change following stimulation of rmSCF and rmNGF and that wortmannin blocks these responses.

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References Cited

  • Arakawa, T., Yphantis, D. A., Lary, J. W., Narhi, L. O., Lu, H. S., Prestrelski, S. J., Clogston, C. L., Zsebo, K. M., Mendiaz, E. A., Wypych, J. and Langley, K. E., Glycosylated and unglycosylated recombinant-derived cell factors are dimeric and have extensive regular secondary structure.J. Biol. Chem., 266, 18942–18948 (1991).

    PubMed  CAS  Google Scholar 

  • Bruni, A., Bigon, E., Boarato, E., Mietto, L., Leon, A. and Toffano, G., Interaction between nerve growth factor and lysophosphatidylserine on rat peritoneal mast cells.FEBS Lett., 138, 190–192 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Cohen, B., Liu, Y., Drucker B., Roberts, T. M. and Schaffhauser, B. S., Characterization of pp85, a target of oncogenes and growth factor receptors.Mol. Cell Biol., 10, 2909–2915 (1990).

    PubMed  CAS  Google Scholar 

  • Columbo, M., Horowitz, E. M., Botana, L. M., MacGlashan, D. W., Jr, Bochner, B., Gillis, S., Zsebo, K. M., Galli, S. J. and Lichtenstein, L. M., The human recombinantc-kit receptor ligand, rhSCF, induces mediator release from human cutaneous mast cells and enhances IgE-dependent mediator release from both skin mast cells and peritoneal blood basophils.J. Immunol., 149, 599–608 (1992).

    PubMed  CAS  Google Scholar 

  • Crawley, J. B., Williams, L. M., Mander, Tom, Brennan, F. M. and Foxwell, B. M., Interleukin-10 stimulation of phosphatidylinositol 3-kinase and p70 S6 kinase is required for the proliferative but not the antiin-flammatory effects of the cytokine.J. Biol. Chem., 271, 16357–16362 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Dastych, J. and Metcalfe, D. D., Stem cell induces mast cell adhesion to fibronectin.J. Immunol., 152, 213–219 (1994).

    PubMed  CAS  Google Scholar 

  • Galli, S. J., New insights into “the riddle of the mast cells” microe nvironmental regulation of mast cell development and phenotypic heterogeneity.Lab. Invest. 62, 5–33 (1990).

    PubMed  CAS  Google Scholar 

  • Galli, S. J., Zsebo, K. M. and Geissler, E. N., The kit ligand, stem cell factor.Adv. Immunol., 55, 1–96 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Huang, E., Nocka K., Beier, D. R., Chu, T.-Y., Buck, J., Lahm, H.-W., Wellner, D., Leder, P. and Besmer, P., The hematopoietic growth factor KL is encoded by SI locus and is the ligand of thec-kit receptor, the gene product of the W locus.Cell, 63, 225–233 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Jullien, D., Tanti, J. F., Heydrick, S. J., Gautier, N., Gremeaux, T., Obberghen, E. Van. and Marchand-Brustel, Y. Le., Differential effects of okadaic acid on insulin-stimulated glucose and amino acid upake and phoshpatidylinositol 3-kinase activity.J. Biol. Chem., 268, 15246–15251 (1993).

    PubMed  CAS  Google Scholar 

  • Kim, H. M., Lee, E. H., Cho, H. H. and Moon, Y. H., Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by spirulina.Biochem. Pharmacol., 55, 1071–1076 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Kitamura, Y., Go, S. and Hatanaka, K., Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation.Blood, 52, 447–452 (1978).

    PubMed  CAS  Google Scholar 

  • Kitamura, Y. and Go, S., Decreased production of mast cells in Sl/Sld anemic mice.Blood, 53, 492–497 (1979).

    PubMed  CAS  Google Scholar 

  • Kundra, V., Escobedo, J. A., Kazlauskas, A., Kim, H. K., Rhee, S. G., williams, L. T. and Zetter, B. R., Regulation of chemotaxis by the platelet-derived growth factor receptor-beta.Nature, 367, 474–476 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Lemura, A., Tsai, M., Ando, A., Wershil, B. K. and Galli, S. J., The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis.Am. J. Pathol., 144, 321–328 (1994).

    Google Scholar 

  • Martrin, F. H., Suggs, S. V., Langley, K. E., Lu, H. S., Ting, J., Okino, K. H., Morris, C. F., McNiece, I. K., Jacobsen, F. W., Mendiaz, E. A., Birkett, N. C., Smith, K. A., Johnson, M. J., Parker, V. P., Flores, J. C., Patel, A. C., Fisher, E. F., Erjavec, H. O., Herrera, C. J., Wypych, J., Sachdev, R. J., Pope, J. A., Leslie, I., Wen, D., Lin, C. H., Cupples, R. L. and Zsebo, K. M., Primary structure and functional expression of rat and human stem cell factor DNAs.Cell, 63, 203–211 (1990).

    Article  Google Scholar 

  • Matsuda, H., Kannan Y., Ushio, H., Kiso, Y., Kanemoto, T., Suzuki, H. and Kitamura, Y., Nerve growth factor induces development of connective tissue-type mast cells in vitro from murine bone marrow cells.J. Exp. Med., 174, 7–14 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Meininger, C. J., Yano, H., Rottapel, R., Bernstein, A., Zsebo, K. M. and Zetter, B. R., The c-kit receptor ligand functions as a mast cell chemoattractant.Blood, 79, 958–963 (1992).

    PubMed  CAS  Google Scholar 

  • Pearce, F. L. and Thompson, H. L., Some characteristic of histamine secretion from rat peritoneal mast cell stimulated with nerve growth factor.J. Physiol. (Lond.), 372, 379–383 (1983).

    Google Scholar 

  • Ruderman, N. B., Kapeller, R., White, M. F. and Cantley, L. C., Activation of phosphatidylinositol 3-kinase by insulin.Proc. Natl. Acad. Sci. USA, 87, 1411–1415 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Snider, W. D. and Johnson, E. M. Jr., Neurotrophic molecules.Ann. Neurol., 26, 489–506 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Valent, P., Sillaber, C. and Bettelheim, P., The growth and differentiation of mast cells.Prog. Growth Factor Res., 3, 27–41 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Williams, D. E., de Vries P., Namen, A. E., Widmer, M. B. and Lyman, S. D., The steel factor.Dev. Biol., 151, 368–376 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Yurt, R. W., Leid, R. W. and Austen, K. F., Native heparin from rat peritoneal mast cells.J. Biol. Chem., 252, 518–521 (1977).

    PubMed  CAS  Google Scholar 

  • Zsebo, K. M., Wypych, J., McNiece, I. K., Lu, H. S., Smith, K. A., Karkare, S. B., Sachdev, R. K., Yuschenkoff, V. N., Birkett, N. C., Williams, L. R., Satyagal, V. N., Tung, W., Bosselman, R. A., Mendiaz, E. A., and Langley, K. E.Cell, 63, 195–201 (1990).

    Article  PubMed  CAS  Google Scholar 

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Kim, HM., Moon, YH. & An, NH. Inhibition of stem cell factor- and nerve growth factor-induced morphological change by wortmannin in mast cells. Arch Pharm Res 22, 108–112 (1999). https://doi.org/10.1007/BF02976532

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