Urothelial cytoprotective activity of Tamm-Horsfall protein isolated from the urine of healthy subjects and patients with interstitial cystitis

Purpose: Tamm-Horsfall protein (THP) is a ubiquitous urinary protein with e ssentially no known function. We propose that THP is a cytoprotective agent that protects the urothelium from cationic species. To test this hypothesi s we isolated THP from normal and interstitial cystitis urine to see if it could protect cultured cells from damage induced by the polyamine, protamin e sulfate (PS). Methods: Tamm-Horsfall protein was extracted from the urine of interstitial cystitis (IC) patients (N = 28) and normal volunteers (N = 5). Urothelial target cells (T24) were radiolabeled with Cr-51 and then exposed to PS (0-1 .0 mg/mL) for either 1.5 or 20 h. The resulting cytotoxicity data (dose-res ponse curves) were then compared with the data obtained when PS was preincu bated with 0-0.5 mg/mL of THP (IC vs normal), the semisynthetic polysacchar ide, pentosan polysulfate (Elmiron), or human serum albumin. Results: Toxicity of PS was significantly reduced by incubation with THP (o r Elmiron) prior to evaluation by the chromium release assay, but not reduc ed by incubating with another protein, albumin. Tamm-Horsfall protein from IC patients' urine was less protective than an equal quantity of THP from n ormal urine. Conclusions: These experiments suggest that THP has an important role in bl adder mucosal defense mechanisms, protecting the bladder surface from injur y. Inability of THP to prevent cytotoxic damage by urinary polyamine or oth er urinary toxins (cationic species) may be relevant in the etiology of int erstitial cystitis, as putative urinary toxic components have been describe d in the urine of some patients.