| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Indiana Center for Biological Microscopy, Department of Medicine, Division of Nephrology, Indiana University, Indianapolis, Indiana
Submitted 20 October 2005 ; accepted in final form 1 December 2005
Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules (proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis.
TLR4; CD14; Tamm-Horsfall protein; cecal ligation and puncture; lipopolysaccharide
This article has been cited by other articles:
|
|
 |
|
  T. M. El-Achkar, X.-R. Wu, M. Rauchman, R. McCracken, S. Kiefer, and P. C. Dagher Tamm-Horsfall protein protects the kidney from ischemic injury by decreasing inflammation and altering TLR4 expression Am J Physiol Renal Physiol, August 1, 2008; 295(2): F534 - F544. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Zhang, G. Ramesh, S. Uematsu, S. Akira, and W. B. Reeves TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity J. Am. Soc. Nephrol., May 1, 2008; 19(5): 923 - 932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yasuda, A. Leelahavanichkul, S. Tsunoda, J. W. Dear, Y. Takahashi, S. Ito, X. Hu, H. Zhou, K. Doi, R. Childs, et al. Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1050 - F1058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Dagher and D. P. Basile An expanding role of Toll-like receptors in sepsis-induced acute kidney injury Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1048 - F1049. [Full Text] [PDF]
|
|
|
|
|
|
T. M. El-Achkar, Z. Plotkin, B. Marcic, and P. C. Dagher Sepsis induces an increase in thick ascending limb Cox-2 that is TLR4 dependent Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1187 - F1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Ramesh, B. Zhang, S. Uematsu, S. Akira, and W. B. Reeves Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice Am J Physiol Renal Physiol, July 1, 2007; 293(1): F325 - F332. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
