THE ROLE OF THE EPITHELIAL-CELL IN ESCHERICHIA-COLI INDUCED NEUTROPHIL MIGRATION INTO THE URINARY-TRACT

Neutrophil influx to mucosal surfaces represents one of the earliest i nflammatory responses to mucosal infection, We have been studying exte rnal interactions with urinary tract epithelial cells in an attempt to understand the molecular mechanisms behind this process. Uropathogeni c Escherichia coil induced urinary tract epithelial cells to secrete t he neutrophil chemoattractant interleukin-8 (IL-8), IL-8 secretion was higher in response to isogenic strains expressing type 1 of P fimbria e that adhered to the epithelial surface, Deliberate colonization of t he human urinary tract with E. coil induced the local production of IL -8 and levels correlated with urinary neutrophil numbers suggesting a role for IL-8 in neutrophil migration. E. coil induced neutrophil migr ation across urinary tract epithelial layers in vitro, and this proces s was blocked with anti-IL-8 antibody, IL-8's activity was localized t o the epithelial surface. Furthermore, these cells were shown to const itutively express IL-8 receptor A and B messenger ribonucleic acid (mR NA), suggesting a possible role for IL-8 on epithelial cell function. E. coli enhanced the expression of intercellular adhesion molecule-1 ( ICAM-1) on urinary tract epithelial cells, and neutrophil migration ac ross urinary tract epithelial layers in vitro was dependent on epithel ial ICAM-1 and neutrophil Mac-1 (CD11b/CD18) expression. These results suggest that bacterial/epithelial cell interactions play a key role i n the induction of neutrophil migration during mucosal infection, and show the necessity for host-derived chemotactic factors and cell adhes ion events in E. coil induced transuroepithelial migration in vitro.