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Blood, 1 August 2008, Vol. 112, No. 3, pp. 493-503. Prepublished online as a Blood First Edition Paper on May 14, 2008; DOI 10.1182/blood-2007-08-108316. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2007-08-108316v1 112/3/493    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 Bonecchi, R. Articles by Locati, M. Search for Related Content PubMed PubMed Citation Articles by Bonecchi, R. Articles by Locati, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 22, 2007 Accepted April 22, 2008 Regulation of D6 chemokine scavenging activity by ligand and Rab11-dependent surface upregulation Raffaella Bonecchi*, Elena M Borroni, Achille Anselmo, Andrea Doni, Benedetta Savino, Massimiliano Mirolo, Monica Fabbri, Venkatakrishna R Jala, Bodduluri Haribabu, Alberto Mantovani, and Massimo Locati Immunology, Istituto Clinico Humanitas IRCCS, Rozzano, Italy Instituto di Patologia Generale, University of Milan, Milan, Italy Unit of Leukocyte Biology, DIBIT-Scientific Institute San Raffaele, Milan, Italy James Graham Brown Cancer Center, University of Louisville Health Sciences, Louisville, KY, United States * Corresponding author; email: raffaella.bonecchi{at}humanitas.it. The decoy receptor D6 plays a non-redundant role in the control of inflammatory processes through scavenging of inflammatory chemokines. However it remains unclear how it is regulated. Here we show that D6 scavenging activity relies on unique trafficking properties. Under resting conditions, D6 constitutively recycled through both a rapid wortmannin (WM)-sensitive and a slower brefeldin A (BFA)-sensitive pathway maintaining low levels of surface expression that required both Rab4 and Rab11 activities. In contrast to "conventional" chemokine receptors that are downregulated by cognate ligands, chemokine engagement induced a dose-dependent BFA-sensitive Rab11-dependent D6 redistribution to the cell membrane and a corresponding increase in chemokine degradation rate. Thus, the energy-expensive constitutive D6 cycling through Rab11 vesicles allows a rapid, ligand concentration-dependent, increase of chemokine scavenging activity by means of receptor redistribution to the plasma membrane. D6 is not regulated at a transcriptional level in a variety of cellular contexts, thus ligand-dependent optimization of its scavenger performance represents a rapid and unique mechanism allowing D6 to control inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Savino, E. M. Borroni, N. M. Torres, P. Proost, S. Struyf, A. Mortier, A. Mantovani, M. Locati, and R. Bonecchi Recognition Versus Adaptive Up-regulation and Degradation of CC Chemokines by the Chemokine Decoy Receptor D6 Are Determined by Their N-terminal Sequence J. Biol. Chem., September 18, 2009; 284(38): 26207 - 26215. [Abstract] [Full Text] [PDF] E. M. Borroni, R. Bonecchi, A. Mantovani, and M. Locati Chemoattractant Receptors and Leukocyte Recruitment: More Than Cell Migration Sci. Signal., February 24, 2009; 2(59): pe10 - pe10. [Abstract] [Full Text] [PDF] A. Mantovani and M. Locati Housekeeping by chemokine scavenging Blood, July 15, 2008; 112(2): 215 - 216. [Full Text] [PDF]

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