RECOMBINANT HUMAN EOTAXIN INDUCES OXYGEN RADICAL PRODUCTION, CA2-MOBILIZATION, ACTIN REORGANIZATION, AND CD11B UP-REGULATION IN HUMAN EOSINOPHILS VIA A PERTUSSIS-TOXIN-SENSITIVE HETEROTRIMERIC GUANINE-NUCLEOTIDE-BINDING PROTEIN()

The novel human CC-chemokine Eotaxin is a potent and selective chemota xin for eosinophils. Here, the biological activities and the activatio n profile of Eotaxin were further characterized and compared with thos e of other eosinophil chemotaxins such as complement fragment C5a (C5a ), platelet-activating factor (PAF), and RANTES in human eosinophils. Eotaxin stimulated the production of reactive oxygen metabolites as sh own by lucigenin-dependent chemiluminescence and superoxide dismutase- inhibitable cytochrome C reduction. Furthermore, Eotaxin induced upreg ulation of the integrin CD11b. In addition, fluorescence measurements with Fura-2-labeled eosinophils in the presence of EGTA indicated Ca2-mobilization from intracellular stores by Eotaxin. Flow cytometric st udies showed rapid and transient actin polymerization on stimulation w ith Eotaxin, At optimal concentrations, the changes induced by Eotaxin were comparable with those obtained by C5a, PAF, and RANTES, Cell res ponses elicited by Eotaxin were inhibited by pertussis toxin, indicati ng coupling of its putative receptor to heterotrimeric guanine nucleot ide-binding proteins, These results indicate that Eotaxin is a strong activator of eosinophils with biological activity comparable with thos e of the eosinophil chemotaxins C5a, PAF, and RANTES. These findings p oint to a role of Eotaxin in the pathogenesis of eosinophilic inflamma tion as a chemotaxin as well as an activator of proinflammatory effect or functions. (C) 1996 by The American Society of Hematology.