Effects of Tamm–Horsfall protein on polymorphonuclear leukocyte function

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2004-09, Vol.19 (9), p.2192-2197
• Main Authors: Wimmer, Thomas, Cohen, Gerald, Saemann, Marcus D., Hörl, Walter H.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; apoptosis; Apoptosis - drug effects; Biological and medical sciences; chemotaxis; Chemotaxis, Leukocyte - drug effects; Emergency and intensive care: renal failure. Dialysis management; Female; Humans; In Vitro Techniques; Intensive care medicine; Male; Medical sciences; Middle Aged; Mucoproteins - pharmacology; Nephrology. Urinary tract diseases; Neutrophils - drug effects; Neutrophils - physiology; phagocytosis; Phagocytosis - drug effects; Pharmacology. Drug treatments; polymorphonuclear leukocytes; Tamm–Horsfall protein; Urinary lithiasis; Urinary system; Uromodulin
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfh206

Background. Tamm–Horsfall protein (THP), a glycoprotein produced exclusively by renal tubular cells, is thought to be involved in several inflammatory disorders such as bacterial interstitial nephritis as well as in defence against uropathogenic microorganisms. The specific effects of THP on inflammatory cells, however, are not yet well known. Therefore, the present study investigates the effects of THP in its soluble form on distinct polymorphonuclear leukocyte (PMNL) functions. Methods. PMNL were isolated from the venous blood of healthy adult donors and incubated at low THP concentrations (70–350 ng/ml), resembling plasma concentrations, and at high THP concentrations (1.75–8.75 µg/ml), resembling urinary concentrations. Results. High (urinary) THP concentrations inhibited PMNL apoptosis and chemotaxis and stimulated PMNL phagocytosis, while low (plasma) THP concentrations increased PMNL chemotaxis. Conclusions. These data indicate that THP influences several PMNL functions, suggesting a crucial immunomodulatory role for this glycoprotein in host defence mechanisms of the kidney and genitourinary tract.