Recent studies have shown that
CC chemokines act on monocytes, lymphocytes, eosinophils and basophils, but not neutrophils, with distinct target cell selectivities, possibly explaining the selective attraction and activation of these cell types in different types of chronic
inflammation and allergic disease. Functional and desensitization studies on basophils and eosinophils indicate the expression of at least three distinct
G-protein-coupled
CC chemokine receptors (three on basophils and two on eosinophils), which exert partially selective and partially overlapping
ligand specificities and also appear to mediate distinct functions despite similar signal transduction pathways. Functional studies with all known six human
CC chemokines show that each
cytokine has a distinct spectrum of bioactivities and target cell profile. Interestingly, overall sequence homologies between the
chemokines are not predictive for the cell function or cell type that a particular
chemokine will preferentially activate, and thus discrete sequence motifs may be important for activating the different
CC chemokine receptors. Using different
chemokine mutants and hybrids between
chemokines, the functional importance of selected individual
amino acids and short motifs are now being analysed. These structure-function studies could also lead to antagonists that have more disease-selective anti-inflammatory properties than currently available drugs.