Heterogeneity of human Fc epsilon RI-bearing cells

Anti-IgE challenge of human basophils and mast cells reveals differences in the arachidonic acid metabolites produced and the biochemical mechanisms of release. Thus the basophil releases only leukotriene C and skin and bronchoalveolar lavage (BAL) mast cells release largely prostaglandin D whereas lung, gut and uterine mast cells generate both products. All cells demonstrate increased Ca2+ levels after excitation but basophils require smaller elevations than mast cells for equivalent release; in spite of this close association, changes in Ca2+ level can be dissociated from histamine release. The importance of protein kinase C activation (assessed by direct measurement, inhibitor studies and/or TPA-induced depletion) in release is variable, being critical in the basophil and showing progressively less importance in skin, lung and BAL mast cells. Different secretagogues utilize distinct biochemical mechanisms in the same mast cell. BAL mast cells are 1000-fold more sensitive and basophils 100-fold more sensitive to anti-IgE than lung, gut or skin mast cells. In keeping with this only BAL mast cells and basophils are sensitive to the IgE-dependent histamine-releasing factors. These in vitro findings accurately predict the observations made in human in vivo antigen challenge systems utilizing the upper and lower airways and the skin. They also provide insight into the pathogenesis of the early and late response to antigen.