Biochemical Cascade Involved in Mast Cell Activation for Mediator Release

  • Teruko Ishizaka
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Mast cells and basophil granulocytes bear specific receptors for IgE, which bind IgE molecules with high affinity, and the reactions of cell-bound IgE antibodies with multivalent antigen initiate the release of a variety of preformed and newly generated mediators such as histamine and leukotrienes (Ishizaka and Ishizaka, 1975). Mast cells also secrete these inflammatory mediators in response to various nonspecific stimuli. These mediators cause allergic disorders in both experimental animals and men. Among the various mast-cell-derived mediators, oxidative products of arachidonic acid (AA) have drawn much attention in recent years. It has been shown that rat peritoneal mast cells and human lung mast cells, but not bone-marrow-derived mouse mast cells, generate prostaglandin D2 (PGD2) through the cyclooxygenase pathway. Conversely, mouse bone-marrow-derived mast cells, as well as human lung mast cells generate primarily leukotriene C4 (LTC4) through the lipoxygenase pathway, but peritoneal mast cells do not (Lewis et al., 1981; Peters et al., 1984; Razin et al., 1983). Leukotrienes cause contraction of airway smooth muscles and are considered to be the most potent bronchoconstrictors in human asthma.


Mast Cell Histamine Release Phosphatidic Acid Mediator Release Human Mast Cell 
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  1. Austen, K.F., and Brocklehurst, W.W., 1960, Anaphylaxis in chopped guinea pig lung. I. Effect of peptidase substrate and inhibitors, J. Exp. Med. 113:521–539.CrossRefGoogle Scholar
  2. Becker, E.L., and Austen, K.F., 1966, Mechanisms of immunologic injury of rat peritoneal mast cells. I. The effect of phosphonate inhibitors on homocytotropic antibody-mediated histamine release and the first component of rat complement, J. Exp. Med. 124:379–395.PubMedCrossRefGoogle Scholar
  3. Conrad, D.H., Froese, A., Ishizaka, T., and Ishizaka, K., 1978, Evidence for antibody activity against the receptor for IgE in a rabbit antiserum prepared against IgE-receptor complexes, J. Immunol. 120:507–512.PubMedGoogle Scholar
  4. Hirata, F., and Axelrod, J.A., 1978, Enzymatic synthesis and rapid translocation of phosphatidylcholine by two methyltransferases in erythrocyte membranes, Proc. Nad. Acad. Sci. U.S.A. 75:2348–2352.CrossRefGoogle Scholar
  5. Holgate, S., Lewis, R., and Austen, K.F., 1980, Role of adenylate cyclase in immunologie release of mediators from rat mast cells. Agonist and antagonist effect of purine and ribose-modified adenosine analogs, Proc. Natl. Acad. Sci. U.S.A. 77:6800–6804.PubMedCrossRefGoogle Scholar
  6. Ishizaka, T., and Ishizaka, K., 1975, Biology of immunoglobulin E, Prog. Allergy 19:60–121.PubMedGoogle Scholar
  7. Ishizaka, T., and Ishizaka, K., 1978, Triggering of histamine release from rat mast cells by divalent antibodies against IgE-receptor, J. Immunol. 120:800–805.PubMedGoogle Scholar
  8. Ishizaka, T., Chang, T.H., Taggart, M., and Ishizaka, K., 1977, Histamine release from mast cells by antibodies against rat basophilic leukemia cell membrane, J. Immunol. 119:1589–1596.PubMedGoogle Scholar
  9. Ishizaka, T., Hirata, F., Ishizaka, K., and Axelrod, J.A., 1979, Induction of calcium influx across the rat mast cell membrane by bridging IgE receptors, Proc. Natl. Acad. Sci. U.S.A. 76:5858–5862.PubMedCrossRefGoogle Scholar
  10. Ishizaka, T., Hirata, F., Sterk, A.R., Ishizaka, K., and Axelrod, J.A., 1981, Bridging of IgE receptors activates phospholipid methylation and adenylate cyclase in mast cell plasma membrane, Proc. Natl. Acad. Sci. U.S.A. 78:6812–6816.PubMedCrossRefGoogle Scholar
  11. Ishizaka, T., Conrad, D.H., Schulman, D.S., Sterk, A.R., and Ishizaka, K., 1983, Biochemical analysis of initial triggering events of IgE-mediated histamine release from human lung mast cells, J. Immunol. 130:2357–2362.PubMedGoogle Scholar
  12. Kennerly, D.A., Sullivan, T.J., and Parker, C.W., 1979, Activation of phospholipid metabolism during mediator release from stimulated rat mast cells, J. Immunol. 122:152–159.PubMedGoogle Scholar
  13. Lewis, R.A., Holgate, S.T., Roberts, L.J., II, Maguire, J.F., Oates, J.A., and Austen, K.F., 1979, Effect of indomethacine on cyclic nucleotide levels and histamine release from rat serosal mast cells, J. Immunol. 123:1633–1638.Google Scholar
  14. Lewis, R. A., Holgate, S. T., Roberts, L. J., II, Oates, J. A., and Austen, K. F., 1981, Preferential generation of prostaglandin D2 by rat and human mast cells, in: Biochemistry of the Acute Allergic Reactions (E. L. Becker, A. S. Simon, and K. F. Austen, eds.), Alan R. Liss, New York, pp. 239–254.Google Scholar
  15. McGivney, A., Crew, F.T., Hirata, F., Axelrod, J.A., and Siraganian, R.P., 1981, Rat basophilic leukemia cell lines defective in phospholipid methyltransferase enzymes, Ca2+ influx and histamine release, Reconstitution by hybridization, Proc. Natl. Acad. Sci. U.S.A. 78:6176–6180.PubMedCrossRefGoogle Scholar
  16. Ogawa, M., Nakahata, T., Leary, A.G., Sterk, A.R., Ishizaka, K., and Ishizaka, T., 1983, Suspension culture of human mast cells/basophils from umbilical cord blood mononuclear cells, Proc. Natl. Acad. Sci. U.S.A. 80:4494–4498.PubMedCrossRefGoogle Scholar
  17. Peters, S.P., MacGlashan, D.W., Jr., Schulman, E.S., Schleimer, R.P., Hayes, E.C, Rokach, J., Adkinson, N.F., Jr., and Lichtenstein, L.M., 1984, Arachidonic acid metabolism in purified human lung mast cells, J. Immunol. 132:1972–1979.PubMedGoogle Scholar
  18. Razin, E., Mencia-Huerta, J.M., Stevens, R.L., Lewis, R.A., Liu, F.T., Corey, E.J., and Austen, K.F., 1983, IgE-mediated release of leukotriene C4, chrondroitin sulfate E proteoglycan, ß-hexosaminidase and histamine from cultured bone marrow-derived mouse mast cells, J. Exp. Med. 157:189–201.PubMedCrossRefGoogle Scholar
  19. Sullivan, T. J., 1981, Diacylglycerol metabolism and the release of mediators from mast cells, in: Biochemistry of the Acute Allergic Reactions (E. L. Becker, A. S. Simon, and K. F. Austen, eds.), Alan R. Liss, New York, pp. 229–238.Google Scholar
  20. White, J.R., Ishizaka, T., Ishizaka, K., and Sha’afi, R., 1984, Direct demonstration of increased intracellular concentration of free calcium as measured by quin-2 in rat peritoneal mast cell, Proc. Natl. Acad. Sci. U.S.A. 81:3978–3982.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Teruko Ishizaka
    • 1
  1. 1.Subdepartment of ImmunologyThe Johns Hopkins University School of Medicine, Good Samaritan HospitalBaltimoreUSA

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