Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells

In addition to their role as regulators of leukocyte migration and activati on, chemokines and their receptors also function in angiogenesis, growth re gulation, and HIV-1 pathogenesis - effects that involve the action of chemo kines on nonhematopoietic cells. To determine whether chemokine receptors a re expressed in human colonic epithelium, HT-29 cells were examined by RT-P CR for the expression of the chemokine receptors for lymphotactin, fractalk ine, CCR1-10, and CXCR1-5. The only receptor consistently detected was CXCR 4 (fusin/LESTR), although HT-29 cells did not express mRNA for its ligand, stromal cell-derived factor (SDF-1 alpha). Flow cytometric analysis with an ti-CXCR4 antibody indicated that the CXCR4 protein was expressed on the sur face of roughly half of HT-29 cells. CXCR4 was also expressed in colonic ep ithelial cells in vivo as shown by immunohistochemistry on biopsies from no rmal and inflamed human colonic mucosa. The mRNA for SDF-1 alpha and other CC and CXC chemokines was present in normal colonic biopsies. The CXCR4 rec eptor in HT-29 cells was functionally coupled, as demonstrated by the eleva tion in [Ca2+](i), which occurred in response to 25 nM SDF-1 alpha and by t he SDF-1 alpha-induced upregulation of ICAM-1 mRNA. Sodium butyrate downreg ulated CXCR4 expression and induced differentiation of HT-29 cells, suggest ing a role for CXCR4 in maintenance and renewal of the colonic epithelium. This receptor, which also serves as a coreceptor for HIV, may mediate viral . infection of colonic epithelial cells.