Journal of Leukocyte Biology
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A more recent version of this article appeared on January 1, 2008

Published online before print October 10, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0407231

Received for publication April 19, 2007.
Revised August 13, 2007.
Accepted for publication August 29, 2007.

Article

Identification of the scavenger receptors SREC-I, Cla-1 (SR-BI), and SR-AI as cellular receptors for Tamm-Horsfall protein

Katharina Pfistershammer *, Christoph Klauser *, Judith Leitner *, Johannes Stöckl *, Otto Majdic *, Thomas Weichhart {dagger}, Yuri Sobanov *, Valery Bochkov {ddagger}, Marcus Säemann {dagger}, Gerhard Zlabinger *, and Peter Steinberger *@

Institutes of *Immunology, Center of Physiology and Pathophysiology, and {ddagger}Vascular Biology and Thrombosis Research, and {dagger}Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria

@ To whom correspondence should be addressed. E-mail: peter.steinberger{at}meduniwien.ac.at.


  Abstract

Tamm-Horsfall protein (THP) is expressed exclusively in the kidney and constitutes the most abundant protein in urine. An important role for THP in antibacterial host defense but also in inflammatory disorders of the urogenital tract has been suggested. In line with this, THP has been shown recently to potently activate macrophages and dendritic cells (DC) via the TLR4 pathway. We show here that THP interacts specifically with surface structures on DC and provides evidence that they are distinct from TLR4. Using retroviral expression cloning, we have identified one such receptor as the scavenger receptor (SR) expressed by endothelial cells I (SREC-I). In addition, we found that two other receptors for acetylated low-density lipoprotein (AcLDL), namely class A SR I (SR-AI) and CD36 and lysosomal integral membrane protein type II analogous-1 (Cla-1; SR-BI), also serve as receptors for THP. SREC-I/THP interaction is of high affinity (16.8±6.8 nM), whereas Cla-1 and SR-AI have lower affinities for THP (396 nM±114 nM and 802 nM±157 nM, respectively). The interaction of THP with these molecules is fully blocked by AcLDL. However, AcLDL only partially blocks binding of THP to DC, and a series of experiments did not support a role in DC activation for SR interacting with THP and AcLDL. Thus, our data point to the existence of additional receptors for THP, which mediate TLR4-dependent DC activation. Interaction and up-take of THP by SR might play an important role in local host defense and could contribute to inflammatory kidney diseases associated with THP-specific antibody responses.

Key Words: dendritic cell • renal host defense • expression cloning






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Copyright © 2007 by the Society for Leukocyte Biology.