HOST-DEFENSE WITHIN THE URINARY-TRACT .2. SIGNAL-TRANSDUCING EVENTS ACTIVATE THE UROEPITHELIAL DEFENSE

It has been shown previously that the interaction between uroepithelia l cells (UEC) from healthy donors and adherent Escherichia coli suppre sses bacterial growth in vitro. The following study was performed to i nvestigate the nature of membrane signal transduction mechanisms invol ved in this process. UEC/E. coli cocultures were established in the pr esence of substances known to modulate transmembranous signals. Inhibi tion of calcium flux, either by calcium channel-blocking substances or by a calmodulin antagonist, depressed the antibacterial UEC function of ''healthy'' UEC. In contrast, receptor/ligand-induced stimulation o f G-proteins, activation of the adenylate cyclase, and the increase of intracellular cyclic AMP levels by cytoplasmatic phosphodiesterase di d not increase the antibacterial capacity of healthy UEC. However, the antibacterial function of defense-deficient UEC from patients with re current idiopathic urinary tract infection could be reconstituted by t his treatment to almost normal levels. In conclusion, the antibacteria l UEC defense function is activated by transmembranous signals from ba cteria attached to the host cell surface. Activation involves the aden ylate cyclase pathway. Activation of the phosphoinositol pathway may c ontribute to intracellular calcium fluxes.