PMID- 23568778
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20211021
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 7
DP  - 2013 Jul
TI  - 15-Epi-lipoxin A4 inhibits human neutrophil superoxide anion generation by 
      regulating polyisoprenyl diphosphate phosphatase 1.
PG  - 2733-41
LID - 10.1096/fj.12-223982 [doi]
AB  - Regulation of leukocyte activation is critical to limit unintended tissue injury 
      during acute inflammation. On neutrophil activation, polyisoprenyl diphosphate 
      phosphatase 1 (PDP1) rapidly converts presqualene diphosphate to presqualene 
      monophosphate to facilitate cell activation. Lipoxins are potent 
      anti-inflammatory mediators for neutrophils, yet their counterregulatory 
      signaling mechanisms remain to be determined. 15-Epi-lipoxin A4 (15-epi-LXA4) 
      blocked agonist-initiated association of the nicotinamide adenine dinucleotide 
      phosphate oxidase components p47(PHOX) and p22(PHOX) in human neutrophils. 
      15-Epi-LXA4 (0.1-100 nM) inhibited neutrophil superoxide anion (O2(-)) generation 
      in a concentration- and ALX/FPR2 receptor-dependent manner that was disrupted by 
      PDP1-specific antibodies. In differentiated HL60 cells, a myeloid cell line, 
      agonist-initiated O2(-) generation was inhibited by PDP1 siRNA. Recombinant human 
      PDP1 was directly phosphorylated in vitro by select protein kinase C (PKC) 
      isoforms, including PKCbetaII. When neutrophils were exposed to 
      formyl-methionyl-leucyl-phenylalanine (fMLP), PKCbetaII was rapidly phosphorylated 
      and physically associated with PDP1. Agonist-initiated conversion of neutrophil 
      presqualene diphosphate to presqualene monophosphate was blocked by PKCbetaII 
      inhibition. Neutrophil exposure to 15-epi-LXA4 attenuated fMLP triggered PKCbetaII 
      phosphorylation and its interactions with PDP1. Together, these findings indicate 
      that PDP1 serves an integral signaling role in neutrophil proinflammatory 
      responses and as a target for counter-regulatory mediators.
FAU - Carlo, Troy
AU  - Carlo T
AD  - Pulmonary and Critical Care Medicine Division, Brigham and Women's Hospital, 
      Boston, MA 02115, USA.
FAU - Kalwa, Hermann
AU  - Kalwa H
FAU - Levy, Bruce D
AU  - Levy BD
LA  - eng
GR  - P01 GM095467/GM/NIGMS NIH HHS/United States
GR  - R01 HL068669/HL/NHLBI NIH HHS/United States
GR  - HL090927/HL/NHLBI NIH HHS/United States
GR  - HL68669/HL/NHLBI NIH HHS/United States
GR  - R01 HL090927/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130408
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Lipoxins)
RN  - 0 (Polyisoprenyl Phosphates)
RN  - 0 (Recombinant Proteins)
RN  - 0 (lipoxin A4)
RN  - 0 (presqualene monophosphate)
RN  - 11062-77-4 (Superoxides)
RN  - 29849-75-0 (presqualene pyrophosphate)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (CYBA protein, human)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C beta)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.51 (dolichyl-phosphatase)
SB  - IM
MH  - Blotting, Western
MH  - Dose-Response Relationship, Drug
MH  - HL-60 Cells
MH  - Humans
MH  - Lipoxins/*pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - NADPH Oxidases/metabolism
MH  - Neutrophils/*drug effects/metabolism
MH  - Phosphoric Monoester Hydrolases/genetics/*metabolism
MH  - Phosphorylation/drug effects
MH  - Polyisoprenyl Phosphates/metabolism
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase C beta
MH  - RNA Interference
MH  - Recombinant Proteins/metabolism
MH  - Superoxides/*metabolism
PMC - PMC3688747
OTO - NOTNLM
OT  - anti-inflammatory
OT  - inflammation
OT  - lipid mediators
OT  - resolution
EDAT- 2013/04/10 06:00
MHDA- 2013/09/21 06:00
PMCR- 2014/07/01
CRDT- 2013/04/10 06:00
PHST- 2013/04/10 06:00 [entrez]
PHST- 2013/04/10 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
PHST- 2014/07/01 00:00 [pmc-release]
AID - fj.12-223982 [pii]
AID - 12-223982 [pii]
AID - 10.1096/fj.12-223982 [doi]
PST - ppublish
SO  - FASEB J. 2013 Jul;27(7):2733-41. doi: 10.1096/fj.12-223982. Epub 2013 Apr 8.