Basophil and eosinophil activation by CC chemokines.
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.
Weber
M
M
Institute of Immunology and Allergology Inselspital, University of Bern, Switzerland.
Dahinden
C A
CA
D001491:Basophils / Q000187:drug effects* / Q000502:physiology; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000145:classification / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D017997:Leukotriene C4 / Q000378:metabolism; D005810:Multigene Family; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D002630:Chemotactic Factors; D016207:Cytokines; D011994:Recombinant Proteins; D017997:Leukotriene C4