PMID- 28894350
OWN - NLM
STAT- MEDLINE
DCOM- 20180521
LR  - 20181113
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2017
DP  - 2017
TI  - Short-Term Regulation of FcgammaR-Mediated Phagocytosis by TLRs in Macrophages: 
      Participation of 5-Lipoxygenase Products.
PG  - 2086840
LID - 10.1155/2017/2086840 [doi]
LID - 2086840
AB  - TLRs recognize a broad spectrum of microorganism molecules, triggering a variety 
      of cellular responses. Among them, phagocytosis is a critical process for host 
      defense. Leukotrienes (LTs), lipid mediators produced from 5-lipoxygenase (5-LO) 
      enzyme, increase FcgammaR-mediated phagocytosis. Here, we evaluated the participation 
      of TLR2, TLR3, TLR4, and TLR9 in FcgammaR-mediated phagocytosis and whether this 
      process is modulated by LTs. Rat alveolar macrophages (AMs), murine bone 
      marrow-derived macrophages (BMDMs), and peritoneal macrophages (PMs) treated with 
      TLR2, TLR3, and TLR4 agonists, but not TLR9, enhanced IgG-opsonized sheep red 
      blood cell (IgG-sRBC) phagocytosis. Pretreatment of AMs or BMDMs with drugs that 
      block LT synthesis impaired the phagocytosis promoted by TLR ligands, and TLR 
      potentiation was also abrogated in PMs and BMDMs from 5-LO(-/-) mice. LTB(4) 
      production induced by IgG engagement was amplified by TLR ligands, while cys-LTs 
      were amplified by activation of TLR2 and TLR4, but not by TLR3. We also noted 
      higher ERK1/2 phosphorylation in IgG-RBC-challenged cells when preincubated with 
      TLR agonists. Furthermore, ERK1/2 inhibition by PD98059 reduced the phagocytic 
      activity evoked by TLR agonists. Together, these data indicate that TLR2, TLR3, 
      and TLR4 ligands, but not TLR9, amplify IgG-mediated phagocytosis by a mechanism 
      which requires LT production and ERK-1/2 pathway activation.
FAU - Pinheiro, Carla da S
AU  - Pinheiro CDS
AD  - Laboratory of Inflammation, Biophysics Institute Carlos Chagas Filho, Rio de 
      Janeiro, RJ, Brazil.
FAU - Monteiro, Ana Paula T
AU  - Monteiro APT
AD  - Laboratory of Inflammation, Biophysics Institute Carlos Chagas Filho, Rio de 
      Janeiro, RJ, Brazil.
FAU - Dutra, Fabiano F
AU  - Dutra FF
AD  - Department of Immunology, Institute of Microbiology Professor Paulo de Goes, Rio 
      de Janeiro, RJ, Brazil.
FAU - Bozza, Marcelo T
AU  - Bozza MT
AD  - Department of Immunology, Institute of Microbiology Professor Paulo de Goes, Rio 
      de Janeiro, RJ, Brazil.
FAU - Peters-Golden, Marc
AU  - Peters-Golden M
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
FAU - Benjamim, Claudia F
AU  - Benjamim CF
AD  - Laboratory of Immunopharmacology, Biophysics Institute Carlos Chagas Filho, 
      Federal University of Rio de Janeiro, 22541-900 Rio de Janeiro, RJ, Brazil.
FAU - Canetti, Claudio
AU  - Canetti C
AUID- ORCID: 0000-0002-6561-4076
AD  - Laboratory of Inflammation, Biophysics Institute Carlos Chagas Filho, Rio de 
      Janeiro, RJ, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20170815
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Flavonoids)
RN  - 0 (Leukotrienes)
RN  - 0 (TLR3 protein, mouse)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Arachidonate 5-Lipoxygenase/genetics/*metabolism
MH  - Erythrocytes/*drug effects/*metabolism
MH  - Flavonoids/pharmacology
MH  - Immunoblotting
MH  - Leukotrienes/metabolism
MH  - Macrophages, Alveolar/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Phagocytosis/drug effects/genetics/physiology
MH  - Phosphorylation/drug effects/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Sheep
MH  - Toll-Like Receptor 2/genetics/metabolism
MH  - Toll-Like Receptor 3/genetics/metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
PMC - PMC5574301
EDAT- 2017/09/13 06:00
MHDA- 2018/05/22 06:00
PMCR- 2017/08/15
CRDT- 2017/09/13 06:00
PHST- 2017/03/02 00:00 [received]
PHST- 2017/06/08 00:00 [accepted]
PHST- 2017/09/13 06:00 [entrez]
PHST- 2017/09/13 06:00 [pubmed]
PHST- 2018/05/22 06:00 [medline]
PHST- 2017/08/15 00:00 [pmc-release]
AID - 10.1155/2017/2086840 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2017;2017:2086840. doi: 10.1155/2017/2086840. Epub 2017 Aug 
      15.