QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.130161v1 324/1/111    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, L. H. Articles by Edelstein, C. L. Search for Related Content PubMed PubMed Citation Articles by Lu, L. H. Articles by Edelstein, C. L.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Increased Macrophage Infiltration and Fractalkine Expression in Cisplatin-Induced Acute Renal Failure in Mice

Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado

Inflammatory mechanisms contribute to cisplatin-induced acute renal failure (CisARF). Our first aim was to determine renal macrophage infiltration in CisARF. A more than 2-fold increase in CD11b-positive macrophages in the kidney on day 2 preceded the increase in blood urea nitrogen (BUN) and serum creatinine (SCr). Our next aim was to determine the chemoattractant for macrophage infiltration in CisARF. Fractalkine (CX₃CL1) is expressed on activated endothelial cells and is a potent chemoattractant for macrophages that express its receptor (CX₃CR1). Immunoblotting showed that whole-kidney CX₃CL1 expression on days 1, 2, and 3 after cisplatin administration was increased. On immunofluorescence, the intensity of renal endothelial staining of CX₃CL1 in blood vessels was significantly increased on day 2. Circulating von Willebrand factor (vWF), a measure of systemic endothelial injury, was increased on day 2. Next we determined whether macrophages played an injurious role in CisARF. Macrophages were depleted with injections of liposome-encapsulated clodronate (LEC). LEC resulted in a decrease in renal CD11b-positive macrophages on day 3. However, LEC-treated mice were not protected from CisARF on day 3. To determine the role of CX₃CR1, both a specific anti-CX₃ CR1 antibody and CX₃ CR1^–/– mice were used. Administration of the CX₃CR1 antibody and CX₃ CR1^–/– mice was not protected against CisARF. In summary, in CisARF, macrophage infiltration in the kidney, CX₃CL1 expression in whole kidney and blood vessels, and the increase in circulating vWF precede BUN and SCr increase. However, inhibition of macrophage infiltration in the kidney or CX₃CR1 blockade is not sufficient to prevent CisARF.

Address correspondence to: Dr. Charles L. Edelstein, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Box C281, 4200 East 9th Ave., Denver, CO 80262. E-mail: charles.edelstein{at}uchsc.edu

This article has been cited by other articles:

				K. P. Kang, D. H. Kim, Y. J. Jung, A. S. Lee, S. Lee, S. Y. Lee, K. Y. Jang, M. J. Sung, S. K. Park, and W. Kim Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation Nephrol. Dial. Transplant., May 27, 2009; (2009) gfp242v1. [Abstract] [Full Text] [PDF]

				S. B. Campos, S. L. Ashworth, S. Wean, M. Hosford, R. M. Sandoval, M. A. Hallett, S. J. Atkinson, and B. A. Molitoris Cytokine-induced F-actin reorganization in endothelial cells involves RhoA activation Am J Physiol Renal Physiol, March 1, 2009; 296(3): F487 - F495. [Abstract] [Full Text] [PDF]