CUTTING EDGE - DETECTION OF MCP-4 IN DERMAL FIBROBLASTS AND ITS ACTIVATION OF THE RESPIRATORY BURST IN HUMAN EOSINOPHILS

CC-chemokines are an important family of proinflammatory mediators tha t promote the recruitment and activation of human eosinophils in chron ic inflammatory diseases. Recently, a novel human CC-chemokine, monocy te chemotactic protein 4 (MCP-4), has been reported that shows amino a cid sequence similarities with eotaxin and RANTES, induces chemotaxis of eosinophils, and signals through specific chemokine receptors. In t his study, we investigated the effect of MCP-4 on different eosinophil effector functions leading to the activation of the respiratory burst . In human eosinophils, MCP-4 dose dependently induced the production of reactive oxygen species and actin polymerization as a related event . Pretreatment of eosinophils with different enzyme inhibitors interac ting with the signal transduction cascade revealed that Ci protein, pr otein kinase C, tyrosine kinase, and phosphatidylinositol-3-kinase are involved in the signaling following stimulation with MCP-4. In additi on, cytokine-stimulated human dermal fibroblasts expressed high levels of MCP-4 mRNA, suggesting that fibroblasts are a physiologic source o f MCP-4. Therefore, this study demonstrates that there is an important role of MCP-4 in the activation of eosinophils and that the interacti on between dermal fibroblasts and human eosinophils may play an import ant role within the cytokine network.