PMID- 20570963
OWN - NLM
STAT- MEDLINE
DCOM- 20101221
LR  - 20220310
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 24
IP  - 11
DP  - 2010 Nov
TI  - FPR2/ALX receptor expression and internalization are critical for lipoxin A4 and 
      annexin-derived peptide-stimulated phagocytosis.
PG  - 4240-9
LID - 10.1096/fj.10-159913 [doi]
AB  - Lipoxins (LXs) are endogenously produced eicosanoids with well-described 
      anti-inflammatory and proresolution activities, stimulating nonphlogistic 
      phagocytosis of apoptotic cells by macrophages. LXA(4) and the 
      glucocorticoid-derived annexin A1 peptide (Ac2-26) bind to a common 
      G-protein-coupled receptor, termed FPR2/ALX. However, direct evidence of the 
      involvement of FPR2/ALX in the anti-inflammatory and proresolution activity of 
      LXA(4) is still to be investigated. Here we describe FPR2/ALX trafficking in 
      response to LXA(4) and Ac2-26 stimulation. We have transfected cells with 
      HA-tagged FPR2/ALX and studied receptor trafficking in unstimulated, LXA(4) (1-10 
      nM)- and Ac2-26 (30 muM)-treated cells using multiple approaches that include 
      immunofluorescent confocal microscopy, immunogold labeling of cryosections, and 
      ELISA and investigated receptor trafficking in agonist-stimulated phagocytosis. 
      We conclude that PKC-dependent internalization of FPR2/ALX is required for 
      phagocytosis. Using bone marrow-derived macrophages (BMDMs) from mice in which 
      the FPR2/ALX ortholog Fpr2 had been deleted, we observed the nonredundant 
      function for this receptor in LXA(4) and Ac2-26 stimulated phagocytosis of 
      apoptotic neutrophils. LXA(4) stimulated phagocytosis 1.7-fold above basal 
      (P<0.001) by BMDMs from wild-type mice, whereas no effect was found on BMDMs from 
      Fpr2(-/-) mice. Similarly, Ac2-26 stimulates phagocytosis by BMDMs from wild-type 
      mice 1.5-fold above basal (P<0.05). However, Ac2-26 failed to stimulate 
      phagocytosis by BMDMs isolated from Fpr2(-/-) mice relative to vehicle. These 
      data reveal novel and complex mechanisms of the FPR2/ALX receptor trafficking and 
      functionality in the resolution of inflammation.
FAU - Maderna, Paola
AU  - Maderna P
AD  - UCD Diabetes Research Centre, UCD School of Medicine and Medical Science, 
      University College Dublin, Dublin, Ireland.
FAU - Cottell, David C
AU  - Cottell DC
FAU - Toivonen, Tiina
AU  - Toivonen T
FAU - Dufton, Neil
AU  - Dufton N
FAU - Dalli, Jesmond
AU  - Dalli J
FAU - Perretti, Mauro
AU  - Perretti M
FAU - Godson, Catherine
AU  - Godson C
LA  - eng
GR  - 086867/WT_/Wellcome Trust/United Kingdom
GR  - 086867/Z/08/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100622
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Annexins)
RN  - 0 (FPR2 protein, human)
RN  - 0 (Lipoxins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 0 (Receptors, Lipoxin)
RN  - 0 (lipoxin A4)
SB  - IM
MH  - Animals
MH  - Annexins/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - HeLa Cells
MH  - Humans
MH  - Lipoxins/*pharmacology
MH  - Mice
MH  - Microscopy, Confocal
MH  - Peptides/*pharmacology
MH  - Phagocytosis/drug effects
MH  - Protein Transport/drug effects
MH  - Receptors, Formyl Peptide/genetics/*metabolism
MH  - Receptors, Lipoxin/genetics/*metabolism
PMC - PMC4338542
MID - EMS61327
OID - NLM: EMS61327
EDAT- 2010/06/24 06:00
MHDA- 2010/12/22 06:00
PMCR- 2015/02/24
CRDT- 2010/06/24 06:00
PHST- 2010/06/24 06:00 [entrez]
PHST- 2010/06/24 06:00 [pubmed]
PHST- 2010/12/22 06:00 [medline]
PHST- 2015/02/24 00:00 [pmc-release]
AID - fj.10-159913 [pii]
AID - 10.1096/fj.10-159913 [doi]
PST - ppublish
SO  - FASEB J. 2010 Nov;24(11):4240-9. doi: 10.1096/fj.10-159913. Epub 2010 Jun 22.