TY - JOUR
T1 - The pharmacologic modulation of mediator release from human basophils
AU - Warner, Jane A.
AU - MacGlashan, Donald W.
AU - Peters, Stephen P.
AU - Kagey-Sobotka, Anne
AU - Lichtenstein, Lawrence M.
N1 - Funding Information:
From the Department of Medicine, Division of Clinical Immunol-ogy, Johns Hopkins University School of Medicine, Baltimore, Md. Supported by National Institutes of Health Grants AI 20253, AI 20136, and AI 07290. Received for publication Feb. 9, 1987. Accepted for publication March 24, 1988. Reprint requests: Donald W. MacGlashan, Jr., MD, Division of Clinical Immunology, JohnsH opkins University School of Med-icine at The Good Samaritan Hospital, 5601 Loch Raven Blvd., Baltimore, MD 21239. *Recipient of Clinical Investigator Award HL 01034 from National Heart, Lung, and Blood Institute. Current address: Jefferson Medical College, Pulmonary Division, Room 804, College Building, 102 S. Walnut St., Philadelphia, PA 19107. **Recipient of the Pfizer Biomedical ResearchA ward. Publication No. 729 from the O’Neill Laboratories at The Good Samaritan Hospital, Baltimore, MD.
PY - 1988/9
Y1 - 1988/9
N2 - We have characterized the effects of eight different drugs on the IgE-mediated histamine release (HR) and leukotriene C4 (LTC4R) from human basophils. Arachidonic acid analogues 5,8,11 eicosatriynoic acid and 5,8,11,15 eicosatetraynoic acid inhibit the release of both mediators in the range 10-6 to 10-4 mol/L with almost total (80% to 100%) inhibition of release at 10-4 mol/L. The inhibition of LTC4R was significantly (p < 0.05) greater than the inhibition of HR only at intermediate (10-5 to 3 × 10-5 mol/L) doses of the drugs. Two other inhibitors of phospholipase A2 (bromophenacyl bromide and phenidone) affected the release of both mediators equally. Two drugs that activate adenylate cyclase (prostaglandin E1 and dimaprit) inhibited release in a dose-dependent fashion but failed to preferentially affect either HR or LTC4R. Isoproterenol (10-6 to 10-4 mol/L), a third activator of adenylate cyclase, caused only moderate (30%) inhibition of HR, even when the reaction was staged, but was slightly (0.1 < p < 0.05) more potent against leukotriene release. The final drug tested was the phosphodiesterase inhibitor, isobutylmethylxanthine, which proved to be an effective (50% to 100%) inhibitor of both mediators in the range 10-5 to 10-3 mol/L.
AB - We have characterized the effects of eight different drugs on the IgE-mediated histamine release (HR) and leukotriene C4 (LTC4R) from human basophils. Arachidonic acid analogues 5,8,11 eicosatriynoic acid and 5,8,11,15 eicosatetraynoic acid inhibit the release of both mediators in the range 10-6 to 10-4 mol/L with almost total (80% to 100%) inhibition of release at 10-4 mol/L. The inhibition of LTC4R was significantly (p < 0.05) greater than the inhibition of HR only at intermediate (10-5 to 3 × 10-5 mol/L) doses of the drugs. Two other inhibitors of phospholipase A2 (bromophenacyl bromide and phenidone) affected the release of both mediators equally. Two drugs that activate adenylate cyclase (prostaglandin E1 and dimaprit) inhibited release in a dose-dependent fashion but failed to preferentially affect either HR or LTC4R. Isoproterenol (10-6 to 10-4 mol/L), a third activator of adenylate cyclase, caused only moderate (30%) inhibition of HR, even when the reaction was staged, but was slightly (0.1 < p < 0.05) more potent against leukotriene release. The final drug tested was the phosphodiesterase inhibitor, isobutylmethylxanthine, which proved to be an effective (50% to 100%) inhibitor of both mediators in the range 10-5 to 10-3 mol/L.
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U2 - 10.1016/0091-6749(88)90016-4
DO - 10.1016/0091-6749(88)90016-4
M3 - Article
C2 - 2459175
AN - SCOPUS:0023730951
SN - 0091-6749
VL - 82
SP - 432
EP - 438
JO - The Journal of allergy and clinical immunology
JF - The Journal of allergy and clinical immunology
IS - 3 PART 1
ER -