PMID- 23857584
OWN - NLM
STAT- MEDLINE
DCOM- 20131210
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 35
DP  - 2013 Aug 30
TI  - FcgammaR-driven release of IL-6 by macrophages requires NOX2-dependent production of 
      reactive oxygen species.
PG  - 25098-25108
LID - S0021-9258(20)49116-1 [pii]
LID - 10.1074/jbc.M113.474106 [doi]
AB  - Activation of the FcgammaR via antigen containing immune complexes can lead to the 
      generation of reactive oxygen species, which are potent signal transducing 
      molecules. However, whether ROS contribute to FcgammaR signaling has not been studied 
      extensively. We set out to elucidate the role of NADPH oxidase-generated ROS in 
      macrophage activation following FcgammaR engagement using antigen-containing immune 
      complexes. We hypothesized that NOX2 generated ROS is necessary for propagation 
      of downstream FcgammaR signaling and initiation of the innate immune response. 
      Following exposure of murine bone marrow-derived macrophages (BMDMs) to 
      inactivated Francisella tularensis (iFt)-containing immune complexes, we observed 
      a significant increase in the innate inflammatory cytokine IL-6 at 24 h compared 
      with macrophages treated with Ft LVS-containing immune complexes. Ligation of the 
      FcgammaR by opsonized Ft also results in significant ROS production. Macrophages 
      lacking the gp91(phox) subunit of NOX2 fail to produce ROS upon FcgammaR ligation, 
      resulting in decreased Akt phosphorylation and a reduction in the levels of IL-6 
      compared with wild type macrophages. Similar results were seen following 
      infection of BMDMs with catalase deficient Ft that fail to scavenge hydrogen 
      peroxide. In conclusion, our findings demonstrate that ROS participate in 
      elicitation of an effective innate immune in response to antigen-containing 
      immune complexes through FcgammaR.
FAU - Franchini, Anthony M
AU  - Franchini AM
AD  - From the Center for Immunology and Microbial Disease, Albany Medical College, 
      Albany, New York 12208 and.
FAU - Hunt, Danielle
AU  - Hunt D
AD  - From the Center for Immunology and Microbial Disease, Albany Medical College, 
      Albany, New York 12208 and.
FAU - Melendez, J Andres
AU  - Melendez JA
AD  - the College of Nanoscale Science and Engineering, University at Albany-State 
      University of New York, Albany, New York 12203.
FAU - Drake, James R
AU  - Drake JR
AD  - From the Center for Immunology and Microbial Disease, Albany Medical College, 
      Albany, New York 12208 and. Electronic address: DrakeJ@mail.amc.edu.
LA  - eng
GR  - P01 AI056320/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20130715
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Bacterial Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, IgG)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.6.3.- (Cybb protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/genetics/immunology/metabolism
MH  - Bone Marrow Cells/immunology/*metabolism
MH  - Catalase/genetics/immunology/metabolism
MH  - Francisella tularensis/enzymology/genetics/immunology
MH  - Hydrogen Peroxide/immunology/*metabolism
MH  - Immunity, Innate/physiology
MH  - Interleukin-6/genetics/immunology/*metabolism
MH  - Macrophages/immunology/*metabolism
MH  - Membrane Glycoproteins/genetics/immunology/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NADPH Oxidase 2
MH  - NADPH Oxidases/genetics/immunology/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/immunology/metabolism
MH  - Receptors, IgG/genetics/immunology/*metabolism
MH  - Signal Transduction/genetics/immunology
PMC - PMC3757174
OTO - NOTNLM
OT  - Akt
OT  - FC Receptors
OT  - Francisella tularensis
OT  - Macrophages
OT  - NADPH Oxidase
OT  - Reactive Oxygen Species (ROS)
EDAT- 2013/07/17 06:00
MHDA- 2013/12/16 06:00
PMCR- 2014/08/30
CRDT- 2013/07/17 06:00
PHST- 2013/07/17 06:00 [entrez]
PHST- 2013/07/17 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2014/08/30 00:00 [pmc-release]
AID - S0021-9258(20)49116-1 [pii]
AID - M113.474106 [pii]
AID - 10.1074/jbc.M113.474106 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Aug 30;288(35):25098-25108. doi: 10.1074/jbc.M113.474106. Epub 
      2013 Jul 15.