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 accumul ation of the cells in a number of inflammatory diseases. The activity has been shown to be mediated through a specific functional receptor p resent on the surface of neutrophils. No information is available abou t 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 re duced 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 thio l residues are located in the IL-8 binding site of the receptor which are indispensible for normal functions of IL-8.