Int Urogynecol J (1992)3:191-196 9 1992 The International Urogynecology Journal International Urogynecology Journal Review Article The Role of Tamm-Horsfall Protein in the Pathogenesis of Urinary Tract Infection H. H. Reinhart and J. D. Sobel Division of Infectious Diseases, Wayne State University, Detroit, Michigan, and VA Medical Center, Allen Park, Michigan, USA Abstract: Although Tamm-Horsfall protein (THP) has been implicated in a variety of pathologic conditions, its physiologic function still remains unclear. Several studies have shown conclusively that bacteria express- ing mannose-sensitive (MS) fimbriae bind to THP and to THP-coated exfoliated uroepithelial cells. Therefore it has been suggested that THP may prevent MS- fimbriated organisms from colonizing the epithelial surface of the urinary tract. Whereas older clinical studies were often inconclusive, recent studies using more sensitive assays demonstrated reduced THP levels in a geriatric population, in children with urinary tract infections and in elderly women with bacteriuria. Although additional studies are required, available data support a protective role for THP as a non- immune antibacterial host factor against uropathogens. The clinical importance of in vitro studies showing interference of THP with bacterial recognition by leukocytes and down-regulation of cell-mediated im- mune responses is presently unclear. Keywords: Host defenses; Leukocytes; MS-fimbriated bacteria; Tamm-Horsfall protein; Urinary tract infec- tion; Uroepithelial cells Introduction The presence of urinary slime or mucus has been known to nephrologists for many decades. In 1950, Tamm and Horsfall noted the potent inhibitory effect Correspondence and offprint requests to: Harald H. Reinhart, Divi- sion of Infectious Diseases, Harper Hospital, Professional Bldg. North, Suite 202, 4160 John R. St., Detroit, MI 48201, USA. of urine on hemagglutination by influenza, mumps, and Newcastle disease viruses. They were able to isolate the inhibitory substance by simple salt precipitation in 0.58 M NaC1 and determined its glycoprotein nature [1,2]. The physicochemical characteristics of this sub- stance, commonly referred to as uromucoid or Tamm- Horsfall protein (THP), have since then become exten- sively characterized. THP is a fibrillar glycoprotein with an unusually high concentration of complex-type branched carbohydrate side chains [3]. It is present in urine as a highly aggregated macromolecule of several million Daltons, which can be seen as mucous strands on light microscopy. These THP aggregates are com- posed of subunits of approximately 80 kD which associ- ate with each other only by hydrophobic interactions [4]. Recently the gene coding for THP has been sequenced [5]. THP is secreted exclusively by the cells of the ascend- ing limb of the loop of Henle and adjacent convoluted Table 1. Association of THP with renal pathology 1. Acute renal failure (especially in combination with IV-dyes [60]) 2. Promotion/inhibition of kidney stone formation [61] 3. Interstitial nephritis 2~ to VUR [58] or immune-complex disease [62] 4, Interstitial cystitis [63] 5, Balkan nephropathy [64] 6. Renal transplant rejection [65] 7. Marker for renal/extrarenal rhabdoid tumors [66] 8. Elevated autoantibodies to THP in patients with UTI and reflux nephropathy [52] 9. Coating of urinary catheters promoting adherence of E. coli and development of UTI [67] 10. Renal tubular acidosis and autoimmune liver disease [41]