The pharmacologic control of mediator release from human basophils and mast cells.
Insight into the pathogenesis of human allergic and inflammatory disorders has been obtained through a combination of in vitro and in vivo studies. These investigations have demonstrated that human basophils and mast cells release mediators after nonimmunologic as well as immunologic activation in vitro and in vivo: nonimmunologic triggers include changes in osmolarity. Although these cells share many properties, including the presence of high-affinity receptors for IgE on their cell surface, the presence of histamine in granules, the ability to generate and release large quantities of leukotriene C4 (LTC4) after activation, and the ability of several pharmacologic agents including phospholipase inhibitors, acetylene analogues of arachidonic acid (ETYA, ETI), methylxanthines, prostaglandin E2 (PGE2) beta-agonists, and cyclic AMP to inhibit mediator release, they also display notable differences. Human lung mast cells generate and release large quantities of prostaglandin D2 (PGD2) after activation; basophils generate no known cyclooxygenase product. Indomethacin, arachidonic acid, and 5-hydroperoxyeicosatetraenoic acid (5-HPETE) all enhance histamine and LTC4 release from human basophils; no effect is seen with human lung mast cells. Overnight incubation of basophils with glucocorticoids produces a marked inhibition of mediator release; this treatment does not affect the release of mast cell mediators. These in vitro observations are consistent with our in vivo observations and our hypotheses concerning the importance of these cells in allergic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001491:Basophils / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000378:metabolism*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism; D012220:Rhinitis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D013189:SRS-A / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D011457:Prostaglandins D; D013189:SRS-A; D007073:Immunoglobulin E; D006632:Histamine; D015230:Prostaglandin D2