Dansyl cadaverine regulates ligand induced endocytosis of interleukin-8 receptor in human polymorphonuclear neutrophils

Interleukin-8 (IL-8), a neutrophil chemotactic agent, acts as a key mediator in a large number of acute and chronic inflammatory diseases. At 37 degrees C, the receptor for IL-8 is rapidly internalized with its ligand, But no specific inhibitor of this ligand induced internalization of the receptor has been reported so far, We have found that monodansyl cadaverine (MDC) inhibited about 70% of IL-8 induced endocytosis and caused 70% and 66% inhibition of IL-8 mediated chemotaxis and respiratory burst response, respectively, in neutrophils. The uninternalized receptor was detected by anti IL-8R antibody in MDC treated cells. The endocytosis of IL-8R was strongly inhibited under Ca2+ depleted conditions which was restored on addition of 1 mM CaCl2, indicating the critical involvement of a Ca2+ ion in the process. Absence of receptor internalisation makes the MDC treated neutrophils suitable for studying the interaction of IL-8R with potential therapeutic agents e.g. for in vitro screening of anti-inflammatory agents.