FUNCTIONS OF INTERLEUKIN-8 ARE MEDIATED THROUGH THIOL GROUP(S) OF IL-8 RECEPTOR IN HUMAN POLYMORPHONUCLEAR NEUTROPHILS - EFFECTS OF 5,5'-DITHIO-BIS(2-NITROBENZOIC ACID) ON IL-8 RECEPTOR

Interleukin-8, a neutrophil chemotactic agent causes excessive accumulation of the cells in a number of inflammatory diseases. The activity has been shown to be mediated through a specific functional receptor present on the surface of neutrophils. No information is available about the amino acids constituting the IL-8 binding domain of the receptor. Treatment of neutrophils with 5,5'-dithio-bis(2-nitrobenzoic acid), a thiol-specific modifier, at the concentrations of 0.4 mM and 1 mM reduced IL-8 binding ability and IL-8-induced migration of the cells by 45% and 65%, respectively. Dithiothreitol could regenerate the binding capacity and the ligand could protect the receptor from the effect of the reagent. All the evidence suggests that one or more critical thiol residues are located in the IL-8 binding site of the receptor which are indispensible for normal functions of IL-8.