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Blood, 22 January 2009, Vol. 113, No. 4, pp. 963-972. Prepublished online as a Blood First Edition Paper on October 29, 2008; DOI 10.1182/blood-2008-07-170787. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-170787v1 113/4/963    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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Landsman, L. Articles by Jung, S. Search for Related Content PubMed PubMed Citation Articles by Landsman, L. Articles by Jung, S. Related Collections Red Cells, Iron, and Erythropoiesis Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  VASCULAR BIOLOGY CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival Limor Landsman1,*, Liat Bar-On1,*, Alma Zernecke2,*, Ki-Wook Kim1, Rita Krauthgamer1, Erdenechimeg Shagdarsuren2, Sergio A. Lira3, Irving L. Weissman4, Christian Weber2, and Steffen Jung1 1 Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; 2 Institute for Molecular Cardiovascular Research, RWTH University Hospital Aachen, Aachen, Germany; 3 Immunobiology Center, Mount Sinai School of Medicine, New York, NY; and 4 Pathology Department, Stanford University School of Medicine, CA CX3CR1 is a chemokine receptor with a single ligand, the membrane-tethered chemokine CX3CL1 (fractalkine). All blood monocytes express CX3CR1, but its levels differ between the main 2 subsets, with human CD16+ and murine Gr1low monocytes being CX3CR1hi. Here, we report that absence of either CX3CR1 or CX3CL1 results in a significant reduction of Gr1low blood monocyte levels under both steady-state and inflammatory conditions. Introduction of a Bcl2 transgene restored the wild-type phenotype, suggesting that the CX3C axis provides an essential survival signal. Supporting this notion, we show that CX3CL1 specifically rescues cultured human monocytes from induced cell death. Human CX3CR1 gene polymorphisms are risk factors for atherosclerosis and mice deficient for the CX3C receptor or ligand are relatively protected from atherosclerosis development. However, the mechanistic role of CX3CR1 in atherogenesis remains unclear. Here, we show that enforced survival of monocytes and plaque-resident phagocytes, including foam cells, restored atherogenesis in CX3CR1-deficent mice. The fact that CX3CL1-CX3CR1 interactions confer an essential survival signal, whose absence leads to increased death of monocytes and/or foam cells, might provide a mechanistic explanation for the role of the CX3C chemokine family in atherogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fractalkine: one chemokine, many functions Gemma E. White and David R. Greaves Blood 2009 113: 767-768. [Full Text] [PDF] This article has been cited by other articles: O. Soehnlein, L. Lindbom, and C. Weber Mechanisms underlying neutrophil-mediated monocyte recruitment Blood, November 19, 2009; 114(21): 4613 - 4623. [Abstract] [Full Text] [PDF] G. E. White, T. C.C. Tan, A. E. John, C. Whatling, W. L. McPheat, and D. R. Greaves Fractalkine has anti-apoptotic and proliferative effects on human vascular smooth muscle cells via epidermal growth factor receptor signalling Cardiovasc Res, November 12, 2009; (2009) cvp341v2. [Abstract] [Full Text] [PDF] E. L. Gautier, C. Jakubzick, and G. J. Randolph Regulation of the Migration and Survival of Monocyte Subsets by Chemokine Receptors and Its Relevance to Atherosclerosis Arterioscler Thromb Vasc Biol, October 1, 2009; 29(10): 1412 - 1418. [Abstract] [Full Text] [PDF]

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