EFFECTS OF ESCHERICHIA-COLI AND ESCHERICHIA-COLI LIPOPOLYSACCHARIDES ON THE FUNCTION OF HUMAN URETERAL EPITHELIAL-CELLS CULTURED IN SERUM-FREE MEDIUM

Escherichia coli is the microorganism most commonly isolated from huma n urinary tract infections. Earlier studies by others have shown that bacterial attachment and production of toxins (e.g., lipopolysaccharid es [LPS]) enhance recruitment of leukocytes to the infection site and mucosal inflammation. The mechanisms by which these changes occur have not been completely defined. In the present study, epithelial cell cu ltures isolated from the human ureter (UT cells) (A. Elgavish, J. J. W ille, F. Rahemtulla, and L. Debro, Am. J. Physiol. 261:C916-C926, 1991 ; J. J. Wille, J. Park, and A. Elgavish, J. Cell. Physiol. 150:52-58, 1992) served as a model system with which to explore the mechanisms of action of Escherichia coli and E. coli LPS in UT cells. E. coli adher ed to UT cells and inhibited carrier-mediated sulfate uptake to half o f that in untreated UT cells, suggesting that the intracellular pool o f sulfate available for sulfation may be lower in infected cells and m ay lead to the production of undersulfated glycoconjugates. Incubation of UT cells with E. coli LPS inhibited carrier-mediated sulfate uptak e to an extent similar to that caused by whole E. coli, indicating tha t the effect of E. coli on sulfate uptake may be mediated by LPS. LPS caused an increase in Na+ content in rapidly proliferating UT cells bu t not in quiescent cells. We postulated that this change in the intrac ellular ionic environment or changes coupled to it (e.g., pH or Ca2+ l evels) may serve as a transducing signal. This possibility was support ed by the fact that LPS stimulated clustering of ICAM-1 on the cell su rface of rapidly proliferating but not quiescent UT cells. This study suggests that, in vivo, LPS stimulation of ICAM-1 clustering on the su rface of the urothelium may allow more effective binding of leukocytes . This may be the mechanism underlying earlier findings in vivo indica ting a role for LPS in the recruitment of leukocytes to the urinary tr act as a host defense mechanism following urinary tract infection.