Complement and IgE-mediated release of histamine from basophils in vitro. V. Differential effects of drugs modulating arachidonic acid metabolism

J. Farnam, J. A. Grant, M. A. Lett-Brown, C. Hunt, D. O. Thueson, P. C. Giclas

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13 Scopus citations

Abstract

Basophil degranulation probably plays a significant role in the PATHOGENESIS OF DIFFERENT HYPERSENSITIVITY REACTIONS. THESE CELLS CAN BE stimulated to secrete lysosomal histamine in vitro in response to various secretagogues. We compared the effects of drugs, modulating arachidonic acid (AA) metabolism, on histamine release (HR) from human basophils stimulated by anti-IgE antibody or C5a anaphylatoxin. Leukocytes from normal donors were preincubated with drug for 15 min at 22°C, followed by the addition of C5a or anti-IgE for 30 min at 37°C. Bromophenacyl bromide, an inhibitor of AA formation by phospholipase, blocked the effects of C5a and anti-IgE (≥3.3 x 10-6 M, p < 0.05 and p < 0.01, respectively). 3-Amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C, ≥3.3 x 10-5 M) and 5, 8, 11, 14-eicosatetraynoic acid (≥3.3 x 10-4 M), known inhibitors of both cyclooxygenase (COX) and lipoxygenase (LPX) pathways of AA metabolism, blocked both C5a- and anti-IgE-induced HR (p < 0.01). Nordihydroguaiaretic acid, an inhibitor of LPX, decreased HR induced by anti-IgE (≥3.3 x 10-6 M, p < 0.01) and allergens, but reduced C5a-initiated HR only at a higher concentration (≥7 x 10-5 M, p < 0.01). Indomethacin (INDO), an inhibitor of COX, significantly reduced HR caused by C5a (≥3.3 x 10-8 M, p < 0.01) and its degradation product C5a(desArg), but had no effect or caused slight enhancement of HR initiated by anti-IgE. We confirmed that INDO augments allergen-induced HR. Our findings suggest that there are basic differences in the regulation of C5a- and IgE-mediated basophil degranulation.

Original languageEnglish (US)
Pages (from-to)541-547
Number of pages7
JournalJournal of Immunology
Volume134
Issue number1
StatePublished - Mar 6 1985

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Farnam, J., Grant, J. A., Lett-Brown, M. A., Hunt, C., Thueson, D. O., & Giclas, P. C. (1985). Complement and IgE-mediated release of histamine from basophils in vitro. V. Differential effects of drugs modulating arachidonic acid metabolism. Journal of Immunology, 134(1), 541-547.