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1 Department of Medicine, Temple University School of Medicine, Philadephia, PA, USA
2 Department of Anatomy, Temple University School of Medicine, Philadephia, PA, USA
3 Department of Microbiology and Immunology, Temple University School of Medicine, Philadephia, PA, USA
* To whom correspondence should be addressed. E-mail: Kelsen{at}temple.edu.
Activation of the chemokine receptor, CXCR3, by its cognate ligands induces several differentiated cellular responses important to the growth and migration of a variety of
hematopoetic and structural cells. In the human respiratory tract, airway epithelial cells (HAEC) release the CXCR3 ligands, Mig/CXCL9, IP-10/CXCL10, and I TAC/CXCL11. Simultaneous expression of CXCR3 by HAEC would have important implications for the processes of airway
inflammation and repair. Accordingly, in the present study we sought to determine if HAEC also express the classic CXCR3 chemokine receptor (CXCR3-A) and its splice variant (CXCR3- B) and hence, may respond in autocrine fashion to its ligands. We found that cultured HAEC (16-HBE and tracheocytes) constitutively expressed CXCR3 mRNA and protein. CXCR3 mRNA levels assessed by expression array were ~35% of 
-actin expression. In contrast, CCR3,
CCR4, CCR5, CCR8, and CX3CR1 were <5% -actin. Both CXCR3-A and -B were expressed. Furthermore, tracheocytes freshly harvested by bronchoscopy stained positively for CXCR3 by immunofluorescence microscopy and 68% of cytokeratin-positive tracheocytes (i.e., the epithelial cell population) were positive for CXCR3 by flow cytometry. In 16-HBE cells, CXCR3 receptor density (Bmax) was ~78,000 receptors/cell when assessed by competitive
displacement of 125I - labeled IP-10/CXCL10. Finally, CXCR3 ligands induced chemotactic responses and actin reorganization in 16-HBE cells. These findings indicate constitutive expression by HAEC of a functional CXC chemokine receptor, CXCR3. Our data suggest the
possibility that autocrine activation of CXCR3 expressed by HAEC may contribute to airway inflammation and remodeling in obstructive lung disease by regulating HAEC migration.
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