Functional expression of chemokine receptor 2 by normal human eosinophils

Background: Within the granulocytes, the CC chemokines preferentially activ ate basophils and eosinophils on binding to chemokine receptors (CCRs). In vivo administration of neutralizing anti-monocyte chemoattractant protein 1 (MCP-1) antibodies can block accumulation of eosinophils in the lungs of a ntigen-challenged animals. Objective: We studied a panel of chemokines for chemotactic activity in nor mal human eosinophils from healthy donors with a special focus on MCP-1, id entified the respective receptor required for the biological response of eo sinophils, and investigated mediators used for signal transduction. Methods: Cells were enriched by magnetic cell sorting. Receptor expression in cosinophils was shown by RT-PCR and fluorescence-activated cell sorting. The biological response was tested in chemotaxis and calcium mobilization assays. Results: Eosinophils have detectable mRNA for CCR2, and the receptor protei n is expressed on cell surfaces. MCP-1 induces chemotaxis and calcium mobil ization in eosinophils. The chemotactic activity of MCP-1 revealed a double -peaked dose-response curve; one of the peaks is abolished by addition of a blocking antibody to CCR2, but it is insensitive to blocking of CCR1 or CC R3. Specific enzyme inhibitors ruled out signaling characteristics of CCR2 in eosinophils. Conclusion: Normal human eosinophils express functional CCR2 on cell surfac es.