Eotaxin-3/CCL26 Is a Natural Antagonist for CC Chemokine Receptors 1 and 5 A HUMAN CHEMOKINE WITH A REGULATORY ROLE

作者: Vibor Petkovic , Christian Moghini , Samantha Paoletti , Mariagrazia Uguccioni , Basil Gerber

DOI: 10.1074/JBC.M309283200

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摘要: Eotaxin-3 (CCL26), like eotaxin (CCL11) and eotaxin-2 (CCL24), has long been considered a specific agonist for CC chemokine receptor 3 (CCR3), attracting activating eosinophils, basophils, Th2 type T lymphocytes. Although not characterized extensively yet, its expression profile coincides with potential role in allergic inflammation. We recently reported that eotaxin-3 is an antagonist CCR2 (Ogilvie, P., Paoletti, S., Clark-Lewis, I., Uguccioni, M. (2003) Blood 102, 789–784). In the present report, we provide evidence acts as natural on CCR1 -5 well. bound to cells transfected either or well monocytes expressing both receptors. Further, it inhibited chemotaxis, release of free intracellular calcium, actin polymerization when were stimulated known agonists -5. An analysis three-dimensional structure indicated presence two distinct epitopes may be involved binding CCR1, -2, -3, Taken together, our data thus indicate first human features broadband antagonistic activities, suggesting have modulatory rather than inflammatory function. play unrecognized polarization cellular recruitment by lymphocytes eosinophils basophils via CCR3, while concomitantly blocking Th1

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