INTERLEUKIN-8 RECEPTOR OF HUMAN NEUTROPHILS

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Interleukin-8 (IL-8) is a cytokine polypeptide of approximately 8 kDa. IL-8 plays a key role in the migration and localization of neutrophils (PMN) from the peripheral blood to sites of inflammation. The interleukin-8 receptor is a polypeptide made up of approximately 359 amino acids. The receptor is modeled as a rhodopsin-like seven helix membrane-spanning peptide linked to G protein signaling pathways. The aim of this project is to determine the regions of the receptor that are key in binding the IL-8 ligand. We have established a binding assay utilizing 125I radiolabeled IL-8 and whole peripheral human neutrophils. This assay exhibits saturation of the receptor at approximately 1 nM IL-8 and binding is competitively inhibited by excess cold IL-8 (300 nM). Binding studies indicate the presence of both high and low affinity IL-8 receptors on the PMN surface. We have synthesized peptides corresponding to the N-terminal and three extracellular loops of the receptor molecule. We will utilize the above assay and these peptides to determine those regions of the IL-8 receptor that are critical in binding ligand. Key words: Neutrophils-Immunology; Interleukin-8; Receptor Binding