Regulation of cytokine expression and leukotriene formation in human basophils by growth factors, chemokines and chemotactic agonists

Basophils stimulated with IL-3 plus C5a selectively express IL-4 and IL-13 and continuously produce leukotrienes (LT) for hours. C5a combined with IL- 5 or granulocyte-macrophage colony-stimulated factor was, however, much les s effective in promoting cytokine expression and a late continuous phase of LTC4 production, possibly due to lower expression levels of their receptor alpha chains. Basophils also express several chemoattractant receptors, in cluding high levels of C5a receptors, macrophage chemotactic protein (MCP) receptors (CCR2) and eotaxin receptors (CCR3), intermediate levels of CXCR1 , CXCR2 and platelet-activating factor receptors, and lower levels of N-for myl-Met-Leu-Phe (fMLP) receptors. However, among the corresponding agonists , only C5a, fMLP and much more weakly MCP1, were found to induce cytokine e xpression and continuous LTC4 release, and only when combined with IL-3. CC R3, which is highly expressed on basophils and has been shown to mediate st rong migratory but weak release responses, does not regulate cytokine expre ssion. The weakly expressed fMLP receptor is an efficient activator of seve ral cell functions including LTC4 formation, while CXCR2 hardly affects bas ophil function despite considerable expression. Thus, chemoattractant-recep tors mediate different cellular responses unrelated to their expression lev els.