Factors Promoting Histamine and Leukotriene Release

Abstract

Basophils are known to release histamine and leukotrienes in response to IgE dependent and IgE independent agonists. Basophil degranulation and de novo synthesis of lipid mediators are clearly separately regulated. We found that the hematopoietic growth factors IL-3, IL-5, and GM-CSF profoundly modify the basophil response to diverse agonists, without inducing mediator release by themselves. The most potent, on a molar basis, is IL-3. These hematopoietic growth factors, at very low concentrations (a) enhance the releasability to all basophil agonists, (b) change the mediator profile, (c) enhance the rate of mediator release, (d) render basophils responsive to lower agonist concentrations, and (e) render basophils responsive to agonists, which by themselves are unable to activate basophils. Biologically active molecules affecting basophil function can now be divided into four groups according to their capacity to induce basophil degranulation and/or leukotriene generation: 1. complete agonists, 2. partial agonists, 3. incomplete agonists, 4. basophil response modifiers. It may be of particular relevance to the pathogenesis of allergic diseases that the same set of cytokines (IL-3, IL-5, GM-CSF) strongly modifies the function of basophils and eosinophils, the two major effector cell types found in allergic inflammatory sites.