THE INTERLEUKIN-8-RELATED CHEMOTACTIC CYTOKINES GRO-ALPHA, GRO-BETA, AND GRO-GAMMA ACTIVATE HUMAN NEUTROPHIL AND BASOPHIL LEUKOCYTES

GROalpha, a protein structurally related to interleukin-8 (IL-8) and o riginally described as a melanoma growth stimulatory factor, possesses potent neutrophil-stimulating activity. Recently, two closely related genes, grobeta and grogamma, were identified. In the present work, th e three GRO proteins were chemically synthesized, and their biological activities on human neutrophils and other leukocytes were compared. G ROalpha, GRObeta, and GROgamma, like IL-8, induced chemotaxis, shape c hange, a rise in intracellular free calcium levels, exocytosis, and th e respiratory burst in neutrophils. The GRO proteins were also active toward basophils as shown by chemotaxis and intracellular calcium conc entration changes. The order of potency in neutrophils and basophils w as IL-8 > GROalpha greater-than-or-equal-to GROgamma > GRObeta. Of the two IL-8 receptors expressed on human neutrophils, one binds GROalpha with high and the other with low affinity. Competition binding experi ments using radiolabeled IL-8 and GROalpha revealed the same character istics for GRObeta and GROgamma. Similarly, cross-desensitization, as assessed by the stimulus-dependent changes in intracellular calcium co ncentration, indicated that all three GRO proteins interact with commo n receptors. From these results, it can be concluded that GROalpha, GR Obeta, and GROgamma have the same pattern of activity toward human gra nulocytes and that the differences in amino acid sequence among these proteins have only minor effects on biological activity.