ESCHERICHIA-COLI INDUCES TRANSUROEPITHELIAL NEUTROPHIL MIGRATION BY AN INTERCELLULAR-ADHESION MOLECULE-1-DEPENDENT MECHANISM

During bacterial infections at mucosal sites, neutrophils migrate to t he mucosa and cross the epithelial barrier. We have examined neutrophi l migration across Escherichia coli-stimulated uroepithelial cell laye rs in an attempt to more fully understand this process. Stimulation of uroepithelial cells with E. coil or interleukin-1 alpha (IL-1 alpha) induced transepithelial neutrophil migration in a time- and stimulant dose dependent manner. Uroepithelial cell lines and nontransformed uro epithelial cells expressed intercellular adhesion molecule-1 (ICAM-1) but not ICAM-2, E-selectin, or P-selectin. Epithelial ICAM-1 expressio n was enhanced after stimulation with E. coil or IL-1 alpha. Anti-ICAM -1 antibody reduced transepithelial neutrophil migration by 61 to 85%, indicating that neutrophils bound ICAM-1 on the epithelial surface. A ntibodies to CD18 and CD11b reduced migration by 70 to 79%, suggesting that CD11b/CD18 (Mac-1) was acting as the neutrophil receptor for ICA M-1 in this process. Anti-CD11a antibodies had no effect on neutrophil migration. In conclusion, E. coli induced ICAM-1- and Mac-1-dependent transepithelial neutrophil migration. Previous studies have shown tha t urinary tract epithelial cells secrete IL-8 when exposed to E. coil or IL-1 alpha. These observations suggest that epithelial cells play a n active role in neutrophil migration during urinary tract infections.