The CC chemokine receptor antagonist met-RANTES inhibits eosinophil effector functions.
Eosinophils play an important role in allergic diseases such as allergic asthma, rhinoconjunctivitis and atopic dermatitis. Recruitement of eosinophils to the side of inflammation, the release of reactive oxygen species, leading to tissue damage, and the propagation of the inflammatory response are mediated by chemokines. Thus, the applicability of agents able to inhibit or antagonize chemokine-induced eosinophil activation seems to be of interest in the treatment of allergic diseases. Therefore, the effect of the CC chemokine antagonist, Met-RANTES, on its effect on human eosinophil effector functions in response to RANTES, MCP-3 and eotaxin was investigated. Met-RANTES had no intrinsic activity on [Ca2+]i transients in eosinophils and was able to dose-dependently inhibit [Ca2+]i transients in eosinophils following stimulation with RANTES, MCP-3 and eotaxin. Besides its effect on [Ca2+]i transients, Met-RANTES dose-dependently inhibited actin polymerization in eosinophils and the release of reactive oxygen species following stimulation with RANTES, MCP-3 and eotaxin. The results of this study lead to the conclusion that Met-RANTES is an effective and powerful compound to antagonize effector functions of human eosinophils following stimulation with RANTES, MCP-3 and eotaxin and is therefore a promising therapeutic approach to prevent the invasion and destructive power of eosinophils in allergic diseases.
Elsner
J
J
Department of Dermatology, Hannover Medical School, Hannover, Germany. jelsner@csi.com
Petering
H
H
Kimmig
D
D
Wells
T N
TN
Proudfoot
A E
AE
Kapp
A
A
D002118:Calcium / Q000276:immunology; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D054410:Chemokine CCL7; D019742:Chemokines, CC; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000276:immunology / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000276:immunology*
C515456:CCL11 protein, human; C515450:CCL7 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D019742:Chemokines, CC; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; C108335:RANTES, Met-; D019707:Receptors, Chemokine; D002118:Calcium