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) β-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. In vivo nasal challenge of allergic patients with pollen results in immediate symptoms and liberation of the mast cell mediators histamine, PGD2 and LTC4 into nasal secretions. Subjects displaying a late-phase reaction demonstrate a cellular infiltration into the nose and the liberation of histamine, but not PGD2 into nasal secretions. Pretreatment of subjects with glucocorticoids abolishes late phase reactions and the liberation of inflammatory mediators into nasal secretions, without affecting the initial or early response to antigen. These observations suggest that the mast cell and mast cell mediators are primarily responsible for the immediate allergic response and initiate events which lead to late reactions. Late reactions appear to be mediated by other inflammatory cells, perhaps basophils, eosinophils, and neutrophils.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine