DIVERGING SIGNAL-TRANSDUCTION PATHWAYS ACTIVATED BY INTERLEUKIN-8 (IL-8) AND RELATED CHEMOKINES IN HUMAN NEUTROPHILS - IL-8 AND GRO-ALPHA DIFFERENTIALLY STIMULATE CALCIUM INFLUX THROUGH IL-8 RECEPTOR-A AND RECEPTOR-B

Interleukin 8 (IL-8) and Gro-alpha 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-alpha may not be perceived equivalently by neutrophils. I n this study, we have evaluated the effects of IL-8 and Gro-alpha on t he rate of calcium influx in human neutrophils and in 293 cells transf ected with type A or type B IL-8 receptors, Of these two chemokines, o nly Gro-alpha induced an influx of calcium in neutrophils as judged by the sensitivity of the mobilization of calcium to the extracellular c alcium chelator EGTA and to the nonselective divalent cation channel i nhibitor SK&F 96365, as well as by manganese quenching experiments, IL -8 was similarly without effect on the rate of Mn2+ influx in 293 cell s transfected with IL-8 receptor A (IL-8RA) or IL-8RB. On the other ha nd, Gro-alpha 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-alpha but, furthermore, that the consequences of the binding of IL-8 and Gro-alpha to IL-8RB are distinct.