Enhancement of Bacillus Calmette-Guerin Attachment to the Urothelium by Removal of the Rabbit Bladder Mucin Layer

Abstract

It has been established that the urothelial mucin layer functions as a bacterial anti-adherence factor. Intravesical Bacillus Calmette-Guerin is used to treat patients with superficial bladder cancer. The proposed mechanism of action of Bacillus Calmette-Guerin is adherence to the urothelium with induction of an immunologic and/or inflammatory response. The current study was designed to determine if rabbit bladder mucin removal results in increased Bacillus Calmette-Guerin urothelial adherence. PAS and colloidal iron stains were used to demonstrate that intravesical instillation of 50% acetone renders rabbit bladder urothelium mucin deficient. The urothelium remains mucin deficient at two hours, but by 24 hours the mucin layer has been regenerated. Two hours following intravesical 3H-labeled Escherichia coli administration, bacterial adherence was 29-fold greater in mucin deficient than mucin intact rabbits (p = 0.05). By 12 hours, the difference in adherence was not significant. Two hours following intravesical administration of 3H-labeled Bacillus Calmette Guerin, mucosal adherence was 21-fold greater in mucin deficient compared to mucin intact rabbits (p = 0.002). After mucin removal, Bacillus Calmette Guerin urothelial adherence was significantly increased. The significant increase in Bacillus Calmette Guerin adherence after mucin removal may be clinically exploitable.