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Blood, 15 July 2008, Vol. 112, No. 2, pp. 256-263. Prepublished online as a Blood First Edition Paper on March 17, 2008; DOI 10.1182/blood-2007-10-118497. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-10-118497v1 112/2/256    most recent Alert me when this article is cited Alert me if a correction is posted 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 Cardona, A. E Articles by Ransohoff, R. M Search for Related Content PubMed PubMed Citation Articles by Cardona, A. E Articles by Ransohoff, R. M Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 18, 2007 Accepted March 3, 2008 Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues Astrid E Cardona, Margaret E Sasse, Makiko Mizutani, Sandra M Cardona, Liping Liu, Carine Savarin, Taofang Hu, and Richard M Ransohoff* Neuroinflammation Research Center, Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States College of Medicine, University of Cincinnati, Cincinnati, OH, United States Department of Microbiology and Immunology, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Roostown, OH, United States * Corresponding author; email: ransohr{at}ccf.org. In vitro studies have implicated chemokine receptors in consumption and clearance of specific ligands. We studied the role that various signaling chemokine receptors play during ligand homeostasis in vivo. We examined the levels of ligands in serum and CNS tissue in mice lacking chemokine receptors. Compared to receptor-sufficient controls, Cx3cr1-/- mice exhibited augmented levels of CX3CL1 both in serum and brain, and circulating levels of CXCL1 and CXCL2 were increased in Cxcr2-/- mice. CCR2-deficient mice showed significantly increased amounts of circulating CCL2 when compared to wild type mice. Cxcr3-/- mice revealed increased levels of circulating and brain CXCL10 after EAE induction. CCR2-deficient peripheral blood and resident peritoneal cells exhibited reduced binding capacity and biological responses to the CCR1 ligand CCL3, suggesting that elevated levels of CCR2 ligands had down-regulated CCR1. The results indicate that signaling chemokine receptors clear chemokines from circulation and tissues. These homeostatic functions of signaling chemokine receptors need to be integrated into safety and efficacy calculations when considering therapeutic receptor blockade. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Housekeeping by chemokine scavenging Alberto Mantovani and Massimo Locati Blood 2008 112: 215-216. [Full Text] [PDF] This article has been cited by other articles: P. Huang, X. S. Zhao, M. Fields, R. M. Ransohoff, and L. Zhou Imatinib attenuates skeletal muscle dystrophy in mdx mice FASEB J, August 1, 2009; 23(8): 2539 - 2548. [Abstract] [Full Text] [PDF]

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