Chapter 35 - Differential Regulation of Basophil Functions by Chemokines

Abstract

This chapter discusses the differential regulation of basophil functions by chemokines. The first chemokine shown to activate basophils was interleukin-8 (IL-8), despite the fact that IL-8 primarily attracts neutrophil granulocytes. However, IL-8 is a relatively weak basophil chemoattractant, and induces significant mediator release only in basophils primed by IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), or nerve growth factor (NGF). Basophils express particularly high levels of both chemokine receptor type-2 (CCR2) and CCR3. All the ligands for CCR3 are potent chemoattractants for basophils (and eosinophils), but induce significant mediator release only in primed basophils, unless they are also agonists for CCR2. By contrast, CCR2 seems to mediate predominantly mediator release but only weak migratory responses. CCR2 is the only chemokine receptor capable of inducing strong and consistent release responses in blood basophils without the need of priming the cell with a growth factor such as IL-3. Since basophils express several chemokine receptors, of which CCR2 and CCR3 are found at similarly high densities as the C5a receptor, and since chemotactic agonists seem to utilize similar signal transduction pathways, it was reasonable to expect that at least some chemokines may also regulate IL-4 and IL-13 expression. In conclusion, we find that basophils express a particularly broad range of receptors for chemokines and chemotactic agonists. However, each receptor appears to mediate a distinct profile of the different basophil effector functions.