SEARCH:   Advanced

Blood, 1 February 2005, Vol. 105, No. 3, pp. 1127-1134. Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-05-1916. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-05-1916v1 105/3/1127    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yang, L. V Articles by Witte, O. N Search for Related Content PubMed PubMed Citation Articles by Yang, L. V Articles by Witte, O. N Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 19, 2004 Accepted September 13, 2004 Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A Li V Yang, Caius G Radu, Li Wang, Mireille Riedinger, and Owen N Witte* Howard Hughes Medical Institute, Los Angeles, CA, USA Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA Howard Hughes Medical Institute, Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA * Corresponding author; email: owenw{at}microbio.ucla.edu. G2A is a G protein-coupled receptor (GPCR) involved in immune regulation. Previous studies have shown that lysophosphatidylcholine (LPC), a bioactive lipid associated with atherosclerosis and autoimmunity, acts through G2A to induce diverse biological effects. Production of LPC during cell apoptosis serves as a chemotactic signal for macrophage recruitment. Here we demonstrate that macrophage chemotaxis to LPC is dependent on G2A function. Wildtype but not G2A-deficient mouse peritoneal macrophages migrated towards LPC. RNAi mediated knockdown of G2A in J774A.1 macrophages abolished LPC-induced chemotaxis whereas overexpression of G2A significantly enhanced this process. Mutation of the conserved DRY motif of G2A resulted in loss of chemotaxis to LPC, suggesting a requirement for G protein signaling. Unlike most GPCRs, including the chemokine receptors, coupling to Gi is not required for LPC-G2A mediated chemotaxis, but coupling to Gq/11 and G12/13 is necessary as judged by inhibition with dominant negative forms of these alpha subunits or with regulators of G protein signaling (RGS) constructs. Collectively, these data establish that pertussis toxin-insensitive G2A signaling regulates macrophage chemotaxis to LPC. Defects in this signaling pathway may be related to the pathogenesis of systemic autoimmune disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020