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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901131v1 183/4/2356    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Sebastián, C. Articles by Celada, A. PubMed PubMed Citation Articles by Sebastián, C. Articles by Celada, A.

Telomere Shortening and Oxidative Stress in Aged Macrophages Results in Impaired STAT5a Phosphorylation¹

Carlos Sebastián^*, Carmen Herrero^*, Maria Serra^*, Jorge Lloberas^*, María A. Blasco and Antonio Celada^2,*

^* Institute for Research in Biomedicine and University of Barcelona, Barcelona, Spain; and Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, Madrid, Spain

Macrophages are an essential component of both innate and adaptive immunity, and altered function of these cells with aging may play a key role in immunosenescence. To determine the effect of aging on macrophages, we produced bone marrow-derived macrophages in vitro. In these conditions, we analyzed the effect of aging on macrophages without the influence of other cell types that may be affected by aging. We showed that telomeres shorten with age in macrophages leading to a decreased GM-CSF but not M-CSF-dependent proliferation of these cells as a result of decreased phosphorylation of STAT5a. Macrophages from aged mice showed increased susceptibility to oxidants and an accumulation of intracellular reactive oxygen species. In these macrophages STAT5a oxidation was reduced, which led to the decreased phosphorylation observed. Interestingly, the same cellular defects were found in macrophages from telomerase knockout (Terc^–/–) mice suggesting that telomere loss is the cause for the enhanced oxidative stress, the reduced Stat5a oxidation and phosphorylation and, ultimately, for the impaired GM-CSF-dependent macrophage proliferation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a Grant from the MEC BFU 2007-63712/BMC (to A.C.).

² Address correspondence and reprint requests to Prof. Antonio Celada, Institute of Research in Biomedicine, Baldiri Reixac 10, Barcelona Science Park, University of Barcelona, E-08028 Barcelona, Spain. E-mail address: acelada{at}ub.edu

³ Abbreviations used in this paper: ROS, reactive oxygen species; DCF-DA, dichlorofluorescin diacetate; NAC, N-acetylcysteine; WT, wild type.

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The JI 2009 183: 2201-2202. [Full Text]