THE MONOCYTE CHEMOTACTIC PROTEIN-4 INDUCES OXYGEN RADICAL PRODUCTION,ACTIN REORGANIZATION, AND CD11B UP-REGULATION VIA A PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN IN HUMAN EOSINOPHILS

The novel human CC-chemokine monocyte chemotactic protein-4 (MCP-4) is a chemotaxin for eosinophils. Here, the biological activities and the activation profile of MCP-4 was further characterized in eosinophils and compared to other activators such as platelet activating factor (P AF), Eotaxin and RANTES. As demonstrated by lucigenin-dependent chemil uminescence and superoxide dismutase-inhibitable cytochrome C reductio n MCP-4 stimulated the production of reactive oxygen metabolites. Furt hermore, MCP-4 induced up-regulation of the integrin CD11b. Flow cytom etric studies revealed rapid and transient actin polymerization upon s timulation with MCP-4. At optimal concentrations the changes induced b y MCP-4 were weaker than the effects after stimulation with PAF and co mparable to those obtained by RANTES and Eotaxin. Cell responses elici ted by MCP-4 were inhibited by pertussis toxin indicating involvement of G(i)-proteins in this signal pathway. These findings point to a rol e of MCP-4 in the pathogenesis of eosinophilic inflammation as chemota xin as well as activator of pro-inflammatory effector functions. (C) 1 997 Academic Press.