Chemokine stromal cell-derived factor 1α activates basophils by means of CXCR4

Background: The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial cells. CXC chemokine stromal cell-derived factor 1 alpha (SDF-1 alpha) is the only known ligand for CXCR4 To date, the CXCR4 expression and function of SDF-1 alpha in basophils are unknown. Objective: The purpose of this study was to investigate the expression of CXCR4 and functions of SDF-1 alpha in basophils and to characterize the role of the CXCR4-SDF-1 alpha receptor ligand pair in the allergic inflammation. Methods: Basophil purification, flow cytometry, real-time quantitative RT-PCR assay, Northern blotting, intracellular free Ca2+ change, chemotaxis assay, and histamine release assay were used, Results: CXCR4 is abundantly expressed on peripheral blood resting basophils (91%), Likewise, CXCR4 messenger (m)RNA is expressed in resting basophils (3.2 x 10(3) copies per 2 x 10(2) cells). The existence of CXCR4 mRNA was also confirmed in basophils by means of Northern blot analysis. SDF-1 alpha. induces an increase in intracellular free Ca2+ in basophils, SDF-1 alpha activates basophils to chemotaxis (chemotactic index = 3.8) and histamine release (36% of total content) through CXCR4 on the cells. The chemokines SDF-1 alpha, eotaxin, RANTES, monocyte chemoattractant protein (MCP) 1, and macrophage inflammatory protein (MIP) 1 alpha have been demonstrated at different potencies in induction of chemotaxis (eotaxin > SDF-1 alpha > RANTES congruent to MCP-1 >> MIP-1 alpha) and histamine release (MCP-1 congruent to SDF-1 alpha > eotaxin > RANTES > MIP-1 alpha), The optimal concentration seen for SDF-1 alpha effects (chemotaxis and histamine release) on basophils was 100 ng/mL, Conclusion: These results indicate that the CXCR4-SDF-1 alpha receptor ligand pair may be important for the recruitment and activation of the basophils, which is a characteristic effector cell of the allergic inflammation.