Control Mechanisms of Human Basophil Releasability

Extensive evidence suggests that mediator release from inflammatory cells plays a role in the pathogenesis of allergic disorders in humans.‘.2 Most studies have focused on the identification of new mediators de novo synthesized by human inflammatory cells; two such examples are AGEPC and leukotrienes.‘” In addition, a number of laboratories are striving to understand the immunologic and biochemical mechanisms underlying the release of chemical media-. tors.6-8 However, few studies have been devoted to clarifying the pathophysiologic mechanisms that control the release of mediators from human inflammatory cells (i.e., the concept of “releasability”). The concept and the study of releasability in humans originated in the laboratory of Lichtenstein and Conroy’ almost a decade ago. They foresaw that, in addition to quantitative immunologic parameters such as IgE and IgG antibody levels, the study of allergic disorders should include the evaluation of cellular releasability. Until then, releasability was defined on an almost philosophic plane because it was impossible to characterize and separate immunologic from releasability parameters. Schleimer et al.’ selected the basophil system, a reliable experimental model of human anaphylaxis, to initiate the study of releasability. For example, they showed that histamine release is not correlated to the absolute quantity of IgE antibody present on human basophils challenged with the appropriate antigen. 9 ” Similarly, the release of histamine in response to anti-IgE is not related to the number of IgE molecules on the basophil surface.” In addition, they demonstrated that significant differences in IgEand non-&E-mediated releasability exist in some allergic conditions.“-” These pioneering studies supported the notion that basophil releasability is a real entity that could be of some relevance in the pathogenesis of inflammatory disorders. Stimulated by the lack of information on the factors that affect basophil releasability, we initiated a series of investigations to identify and characterize factors that physiologically control basophil releasability. We also used the ba