ABSTRACT
This chapter considers how interleukin-8 (IL-8) may interact with cell-surface receptors on neutrophils. It is clear that IL-8, a CXC chemokine, acts on neutrophils through high-affinity binding to at least two types of receptor, called IL-8 receptor A and IL-8 receptor B. Several studies have addressed the dimerization state of IL-8 in solution, under concentrations presumed to be physiologically relevant. Variants of IL-8 which reduce or enhance the IL-8 dimerization constant offer a means of testing the role of IL-8 dimerization in IL-8 receptor binding and activation, independent of the absolute magnitude of IL-8 dimerization affinity in vitro or in vivo. The stoichiometric picture that emerges from these studies is that IL-8 dimer-ization is not necessary for binding to either receptor A or receptor B, nor for signaling through either of these receptors. The N-terminal domain of the IL-8 receptor has been shown by several investigators to be important for ligand binding.
