Regulation of D6 chemokine scavenging activity by ligand- And Rab 11-dependent surface up-regulation

Raffaella Bonecchi, Elena M. Borroni, Achille Anselmo, Andrea Doni, Benedetta Savino, Massimiliano Mirolo, Monica Fabbri, Venkatakrishna R. Jala, Bodduluri Haribabu, Alberto Mantovani, Massimo Locati

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The decoy receptor D6 plays a nonredundant 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 energyexpensive constitutive D6 cycling through Rab11 vesicles allows a rapid, ligand concentration-dependent increase of chemokine scavenging activity by receptor redistribution to the plasma membrane. D6 is not regulated at a transcriptional level in a variety of cellular contexts, thus liganddependent optimization of its scavenger performance represents a rapid and unique mechanismallowingD6to control inflammation.

Original languageEnglish
Pages (from-to)493-503
Number of pages11
JournalBlood
Volume112
Issue number3
DOIs
Publication statusPublished - Aug 1 2008

Fingerprint

Scavenging
Chemokines
Up-Regulation
Ligands
Brefeldin A
Cell membranes
Cell Membrane
Chemokine Receptors
Down-Regulation
Inflammation
Degradation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Regulation of D6 chemokine scavenging activity by ligand- And Rab 11-dependent surface up-regulation. / Bonecchi, Raffaella; Borroni, Elena M.; Anselmo, Achille; Doni, Andrea; Savino, Benedetta; Mirolo, Massimiliano; Fabbri, Monica; Jala, Venkatakrishna R.; Haribabu, Bodduluri; Mantovani, Alberto; Locati, Massimo.

In: Blood, Vol. 112, No. 3, 01.08.2008, p. 493-503.

Research output: Contribution to journalArticle

Bonecchi, Raffaella ; Borroni, Elena M. ; Anselmo, Achille ; Doni, Andrea ; Savino, Benedetta ; Mirolo, Massimiliano ; Fabbri, Monica ; Jala, Venkatakrishna R. ; Haribabu, Bodduluri ; Mantovani, Alberto ; Locati, Massimo. / Regulation of D6 chemokine scavenging activity by ligand- And Rab 11-dependent surface up-regulation. In: Blood. 2008 ; Vol. 112, No. 3. pp. 493-503.
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