title: Complement- and IgE-mediated release of histamine from basophils in vitro. V. Differential effects of drugs modulating arachidonic acid metabolism.
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 degrees C, followed by the addition of C5a or anti-IgE for 30 min at 37 degrees C. Bromophenacyl bromide, an inhibitor of AA formation by phospholipase, blocked the effects of C5a and anti-IgE (greater than or equal to 3.3 X 10(-6) M, p less than 0.05 and p less than 0.01, respectively). 3-Amino-1-(3-trifluoromethylphenyl)-2-pyrazoline hydrochloride (BW755C, greater than or equal to 3.3 X 10(-5) M) and 5, 8, 11, 14-eicosatetraynoic acid (greater than or equal to 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 less than 0.01). Nordihydroguaiaretic acid, an inhibitor of LPX, decreased HR induced by anti-IgE (greater than or equal to 3.3 X 10(-6) M, p less than 0.01) and allergens, but reduced C5a-initiated HR only at a higher concentration (greater than or equal to 7 X 10(-5) M, p less than 0.01). Indomethacin (INDO), an inhibitor of COX, significantly reduced HR caused by C5a (greater than or equal to 3.3 X 10(-8) M, p less than 0.01) and its degradation product C5adesArg, 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.
authors.forename: J
authors.initials: J
authors.lastname: Farnam
authors.forename: J A
authors.initials: JA
authors.lastname: Grant
authors.forename: M A
authors.initials: MA
authors.lastname: Lett-Brown
authors.forename: C
authors.initials: C
authors.lastname: Hunt
authors.forename: D O
authors.initials: DO
authors.lastname: Thueson
authors.forename: P C
authors.initials: PC
authors.lastname: Giclas
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001491:Basophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D003182:Complement C5 / Q000276:immunology*; D015936:Complement C5a; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol; D010740:Phospholipases / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D002396:Catechols; D003182:Complement C5; D011720:Pyrazoles; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D007073:Immunoglobulin E; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D015936:Complement C5a; D010740:Phospholipases; D007213:Indomethacin