Hepatocyte growth factor alters renal epithelial cell susceptibility to uropathogenic Escherichia coli

The urinary tract is frequently the source of Escherichia coli bacteremia. Bacteria from the urinary tract must cross an epithelial layer to enter the bloodstream. Hepatocyte growth factor (HGF) alters the polarity of Madin-D arby canine kidney (MDCK) epithelial cells. The role of cell polarity in de termining renal epithelial resistance to Escherichia coli invasion is not w ell known. A model of polarized and HGF-treated MDCK epithelial cells grown on filters was used to study the role of epithelial cell polarity during t he interaction of nonvirulent (XL1-Blue) and uropathogenic (J96) strains of Escherichia coli with renal epithelium. Basolateral. exposure of MDCK cell s to J96, but not XL1-Blue, resulted in loss of transepithelial resistance (TER), which was due to epithelial cytotoxicity and not degradation of epit helial junctional proteins by bacterial proteases. Apical exposure to both J96 and XL1-Blue did not alter TER. Pretreatment of polarized MDCK cell mon olayers with HGF renders the cells sensitive to loss of TER and cytotoxicit y by apical exposure to J96. Analysis by confocal microscopy demonstrated t hat HGF treatment of MDCK cell monolayers also greatly enhances adherence o f J96 to the apical surface of the cell monolayer. These data demonstrate t hat the basolateral surface of polarized epithelia is more susceptible to J 96 cytotoxicity. The data also support the hypothesis that processes that a lter epithelial cell polarity increase sensitivity of epithelia to bacteria l injury and adherence from the apical compartment.