2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2006111299v1 18/4/1239    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Wang, P.-X. Articles by Sanders, P. W. Search for Related Content PubMed PubMed Citation Articles by Wang, P.-X. Articles by Sanders, P. W.

Immunoglobulin Light Chains Generate Hydrogen Peroxide

Pei-Xuan Wang^* and Paul W. Sanders^*,,

^* Division of Nephrology, Department of Medicine, and Department of Physiology and Biophysics, University of Alabama at Birmingham, and Department of Veterans Affairs Medical Center, Birmingham, Alabama

Address correspondence to: Dr. Paul W. Sanders, Division of Nephrology/Department of Medicine, 642 Lyons-Harrison Research Building, 1530 Third Avenue, S., University of Alabama at Birmingham, Birmingham, AL 35294-0007. Phone: 205-934-3589; Fax: 205-975-6288; E-mail: psanders{at}uab.edu

Received for publication November 30, 2006. Accepted for publication January 29, 2007.

As low molecular weight proteins, restriction from glomerular filtration is minimized, permitting significant amounts of Ig light chains to be endocytosed into the proximal tubule epithelium, particularly in plasma cell dyscrasias. Recent studies have shown that this effect of concentrating light chains within the proximal tubule alters cell function. This study demonstrated that light chains belonged to a class of proteins that are capable of catalyzing the formation of hydrogen peroxide. Sufficient amounts of hydrogen peroxide were produced in HK-2 cells to stimulate the production of monocyte chemoattractant protein-1 (MCP-1), a key chemokine involved in monocyte/macrophage migration and activation of the proximal tubule, and to increase lactate dehydrogenase release into the medium. The light chain–mediated effect on MCP-1 production was inhibited by co-incubation with 1,3-dimethyl-2-thiourea, which also inhibited lactate dehydrogenase release, and by pyrrolidine dithiocarbamate, an inhibitor of NF-B. The amount of light chain that stimulated an intracellular redox-signaling pathway in the proximal tubule cells was well within levels that are seen in patients who have plasma cell dyscrasias. The conclusion is that light chains possess a unique property that permits the development of intracellular oxidative stress that in turn promotes activation of the proximal tubule and elaboration of MCP-1.

This article has been cited by other articles:

				C. A. Hutchison, S. Harding, P. Hewins, G. P. Mead, J. Townsend, A. R. Bradwell, and P. Cockwell Quantitative Assessment of Serum and Urinary Polyclonal Free Light Chains in Patients with Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., November 1, 2008; 3(6): 1684 - 1690. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673