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 (PAF), Eotaxin and RANTES. As demonstrated by lucigenin-dependent chemiluminescence and superoxide dismutase-inhibitable cytochrome C reduction MCP-4 stimulated the production of reactive oxygen metabolites. Furthermore, MCP-4 induced up-regulation of the integrin CD11b. Flow cytometric studies revealed rapid and transient actin polymerization upon stimulation with MCP-4. At optimal concentrations the changes induced by MCP-4 were weaker than the effects after stimulation with PAF and comparable to those obtained by RANTES and Eotaxin. Cell responses elicited by MCP-4 were inhibited by pertussis toxin indicating involvement of Gi-proteins in this signal pathway. These findings point to a role of MCP-4 in the pathogenesis of eosinophilic inflammation as chemotaxin as well as activator of pro-inflammatory effector functions.