This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kreft, B.
Right arrow Articles by van Zandbergen, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kreft, B.
Right arrow Articles by van Zandbergen, G.

 Previous Article  |  Next Article 

Infection and Immunity, May 2002, p. 2650-2656, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2650-2656.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Polarized Expression of Tamm-Horsfall Protein by Renal Tubular Epithelial Cells Activates Human Granulocytes

B. Kreft,1* W. J. Jabs,1 T. Laskay,2 M. Klinger,3 W. Solbach,2 S. Kumar,4 and G. van Zandbergen2

Department of Internal Medicine, Division of Infectious Diseases,1 Department of Medical Microbiology,2 Department of Anatomy, Medical University of Lübeck, Lübeck, Germany,3 University of Oklahoma and V.A. Medical Center, Oklahoma City, Oklahoma4

Received 27 November 2001/ Accepted 8 January 2002

In renal bacterial infections granulocytes are of major importance in the primary immune defense against invading pathogens. However, the mechanisms of granulocytic activation in renal interstitial invasion have not been clarified. Renal tubular epithelial cell mechanisms inducing granulocytic activation and bacterial killing may include tubular cell expression of Tamm-Horsfall protein (THP), a urinary protein that is known to enhance cytokine expression in monocytes. We studied the role of THP in granulocytic activation. A strong binding of THP to human granulocytes was demonstrated by fluorescence-activated cell sorter analysis. Urinary THP and supernatants of THP-expressing cultured tubular epithelial cells (MDCK) enhanced interleukin-8 (IL-8) expression by human granulocytes. Renal tubular cells growing polarized on polycarbonate membranes were used to study apical versus basal THP expression. By electron microscopy THP immunoreactivity was exclusively found on the apical surfaces of tubular cells and was absent on the basolateral cell membrane. In the apical cell culture compartment we found significantly more stimulatory activity for granulocytic IL-8 expression. CD62L, a selectin less expressed in activated granulocytes, was decreased in granulocytes incubated with urinary THP and in supernatants of THP-producing renal tubular cells but not in supernatants from THP-negative cells. Again, the effect on CD62L expression was found only in apical culture media and was absent in the basal compartment. In summary our data give evidence that renal tubular cell THP expression may be relevant in kidney diseases since THP is a potent activator of human granulocytes. The regulation of apical versus basal THP expression and release in vivo may be crucial in the induction of the inflammatory response, e.g., in bacterial renal diseases.

* Corresponding author. Mailing address: Department of Internal Medicine, Medical University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Phone: 49 451 500 2336. Fax: 49 451 500 3339. E-mail: B-KREFT{at}gmx.de.

Editor: A. D. O'Brien

Infection and Immunity, May 2002, p. 2650-2656, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2650-2656.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pfistershammer, K., Klauser, C., Leitner, J., Stockl, J., Majdic, O., Weichhart, T., Sobanov, Y., Bochkov, V., Saemann, M., Zlabinger, G., Steinberger, P. (2008). Identification of the scavenger receptors SREC-I, Cla-1 (SR-BI), and SR-AI as cellular receptors for Tamm-Horsfall protein. J. Leukoc. Biol. 83: 131-138 [Abstract] [Full Text]  
  • Kumar, S. (2007). Mechanism of Injury in Uromodulin-Associated Kidney Disease. J. Am. Soc. Nephrol. 18: 10-12 [Full Text]  
  • Jennings, P., Aydin, S., Kotanko, P., Lechner, J., Lhotta, K., Williams, S., Thakker, R. V., Pfaller, W. (2007). Membrane Targeting and Secretion of Mutant Uromodulin in Familial Juvenile Hyperuricemic Nephropathy. J. Am. Soc. Nephrol. 18: 264-273 [Abstract] [Full Text]  
  • Watts, R.W.E. (2005). Idiopathic urinary stone disease: possible polygenic aetiological factors. QJM 98: 241-246 [Full Text]  
  • Wimmer, T., Cohen, G., Saemann, M. D., Horl, W. H. (2004). Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function. Nephrol Dial Transplant 19: 2192-2197 [Abstract] [Full Text]  
  • Rampoldi, L., Caridi, G., Santon, D., Boaretto, F., Bernascone, I., Lamorte, G., Tardanico, R., Dagnino, M., Colussi, G., Scolari, F., Ghiggeri, G. M., Amoroso, A., Casari, G. (2003). Allelism of MCKD, FJHN and GCKD caused by impairment of uromodulin export dynamics. Hum Mol Genet 12: 3369-3384 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»