Functional expression of chemokine receptor CXCR4 on human epithelial cells

Chemokines and their receptors play an important role in the process of leu cocyte recruitment: at sites of inflammation. However, recent evidence sugg ests that these proteins can also regulate non-leucocyte cell functions suc h as angiogenesis, migration and proliferation. We have investigated the ex pression of the CXC chemokine receptor 4 (CXCR4) on primary cultures of typ e II alveolar epithelial cells, their transformed counterpart, the A549 cel l line and also on other epithelial cell lines from various tissues. We fou nd that all epithelial cell types tested express mRNA for CXCR4. Flow cytom etric analysis and immunocytochemical staining shows that CXCR4 chemokine r eceptor is abundantly expressed on the surface of A549 epithelial cells. Fu rthermore, A549 cells responded to the CXCR4 ligand, stromal-derived factor -1 alpha (SDF-1 alpha) with a rapid and robust calcium mobilization and not to other CXC chemokines, suggesting that CXCR4 is functionally active and is able to couple to G-protein signalling mechanisms. A549 cells did not pr oliferate in response to either SDF-1 alpha or interleukin-8 (IL-8) CXC che mokines. These findings may have important implications for epithelial phys iology and pathology.