Diverging signal transduction pathways activated by interleukin 8 and related chemokines in human neutrophils II: IL-8 and Groa differentially stimulate calium influx through IL-8 receptors A & B

Abstract

Interleukin 8 (IL-8) and Gro-α are members of the CXC branch of a family of cytokines recently designated the “chemokine” superfamily. Recent evidence indicates that, contrary to previously held beliefs, IL-8 and Gro-α may not be perceived equivalently by neutrophils. In this study, we have evaluated the effects of IL-8 and Gro-α on the rate of calcium influx in human neutrophils and in 293 cells transfected with type A or type B IL-8 receptors. Of these two chemokines, only Gro-α induced an influx of calcium in neutrophils as judged by the sensitivity of the mobilization of calcium to the extracellular calcium chelator EGTA and to the nonselective divalent cation channel inhibitor SK&F 96365, as well as by manganese quenching experiments. IL-8 was similarly without effect on the rate of Mn²⁺ influx in 293 cells transfected with IL-8 receptor A (IL-8RA) or IL-8RB. On the other hand, Gro-α induced an SK&F 96365-sensitive increase of the rate of Mn⁺² influx in IL-8RB-, but not in IL-8RA-transfected 293 cells. These results indicate not only that neutrophils respond differently to IL-8 than they do to Gro-α but, furthermore, that the consequences of the binding of IL-8 and Gro-α to IL-8RB are distinct.