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 language | English |
|---|---|
| Pages (from-to) | 493-503 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 112 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Aug 1 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Regulation of D6 chemokine scavenging activity by ligand- And Rab 11-dependent surface up-regulation
AU - Bonecchi, Raffaella
AU - Borroni, Elena M.
AU - Anselmo, Achille
AU - Doni, Andrea
AU - Savino, Benedetta
AU - Mirolo, Massimiliano
AU - Fabbri, Monica
AU - Jala, Venkatakrishna R.
AU - Haribabu, Bodduluri
AU - Mantovani, Alberto
AU - Locati, Massimo
PY - 2008/8/1
Y1 - 2008/8/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2007-08-108316
DO - 10.1182/blood-2007-08-108316
M3 - Article
VL - 112
SP - 493
EP - 503
JO - Blood
JF - Blood
SN - 0006-4971
IS - 3
ER -