Structural and functional characterization of the interleukin-8 receptors

Interleukin-8 (IL-8), growth regulatory gene/melanoma growth stimulatory activity (GRO/MGSA) and neutrophil activating peptide-2 (NAP-2) are members of a growing superfamily of cytokine polypeptides with sequence and structural homology (reviewed in Oppenheim et al., 1991). Four cysteines are conserved in these molecules which may serve to maintain their structural integrity. The three-dimensional structure of IL-8 has been solved by both NMR spectroscopy and x-ray crystallography. IL-8 exists as a homodimer which may undergo conformational changes upon receptor binding (6). Biological studies utilizing recombinant chemotactic peptides have illustrated several distinct functions for these cytokines. Neutrophils respond chemotactically by migrating toward IL-8, GRO/MGSA and NAP-2 (38, 25, 32). Additionally, neutrophil-endothelial cell adhesion has been observed to be enhanced by IL-8 (14), and both IL-8 and GRO/MGSA have been shown to induce a rise in cytosolic-free calcium ([Ca++]i) (25). Melanoma cells have also been reported to show autocrine growth regulation by GRO/MGSA (30).