The role of the epithelial cell in Escherichia coli induced neutrophil migration into the urinary tract.

Abstract

Neutrophil influx to mucosal surfaces represents one of the earliest inflammatory responses to mucosal infection. We have been studying external interactions with urinary tract epithelial cells in an attempt to understand the molecular mechanisms behind this process. Uropathogenic Escherichia coli induced urinary tract epithelial cells to secrete the neutrophil chemoattractant interleukin-8 (IL-8). IL-8 secretion was higher in response to isogenic strains expressing type 1 or P fimbriae that adhered to the epithelial surface. Deliberate colonization of the human urinary tract with E. coli induced the local production of IL-8 and levels correlated with urinary neutrophil numbers suggesting a role for IL-8 in neutrophil migration. E. coli induced neutrophil migration across urinary tract epithelial layers in vitro, and this process was blocked with anti-IL-8 antibody. IL-8's activity was localized to the epithelial surface. Furthermore, these cells were shown to constitutively express IL-8 receptor A and B messenger ribonucleic acid (mRNA), 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 across urinary tract epithelial layers in vitro was dependent on epithelial ICAM-1 and neutrophil Mac-1 (CD11b/CD18) expression. These results suggest that bacterial/epithelial cell interactions play a key role in the induction of neutrophil migration during mucosal infection, and show the necessity for host-derived chemotactic factors and cell adhesion events in E. coli induced transuroepithelial migration in vitro.