PMID- 31316511
OWN - NLM
STAT- MEDLINE
DCOM- 20201021
LR  - 20210312
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Plasminogen and the Plasminogen Receptor, Plg-R(KT), Regulate Macrophage 
      Phenotypic, and Functional Changes.
PG  - 1458
LID - 10.3389/fimmu.2019.01458 [doi]
LID - 1458
AB  - Inflammation resolution is an active process that functions to restore tissue 
      homeostasis. Clearance of apoptotic leukocytes by efferocytosis at inflammatory 
      sites plays an important role in inflammation resolution and induces remarkable 
      macrophage phenotypic and functional changes. Here, we investigated the effects 
      of deletion of either plasminogen (Plg) or the Plg receptor, Plg-R(KT), on the 
      resolution of inflammation. In a murine model of pleurisy, the numbers of total 
      mononuclear cells recruited to the pleural cavity were significantly decreased in 
      both Plg(-/-) and Plg-R(KT)(-/-) mice, a response associated with decreased 
      levels of the chemokine CCL2 in pleural exudates. Increased percentages of 
      M1-like macrophages were determined in pleural lavages of Plg(-/-) and 
      Plg-R(KT)(-/-) mice without significant changes in M2-like macrophage 
      percentages. In vitro, Plg and plasmin (Pla) increased CD206/Arginase-1 
      expression and the levels of IL-10/TGF-beta (M2 markers) while decreasing 
      IFN/LPS-induced M1 markers in murine bone-marrow-derived macrophages (BMDMs) and 
      human macrophages. Furthermore, IL4-induced M2-like polarization was defective in 
      BMDMs from both Plg(-/-) and Plg-R(KT)(-/-) mice. Mechanistically, Plg and Pla 
      induced transient STAT3 phosphorylation, which was decreased in Plg(-/-) and 
      Plg-R(KT)(-/-) BMDMs after IL-4 or IL-10 stimulation. The extents of expression 
      of CD206 and Annexin A1 (important for clearance of apoptotic cells) were reduced 
      in Plg(-/-) and Plg-R(KT)(-/-) macrophage populations, which exhibited decreased 
      phagocytosis of apoptotic neutrophils (efferocytosis) in vivo and in vitro. Taken 
      together, these results suggest that Plg and its receptor, Plg-R(KT), regulate 
      macrophage polarization and efferocytosis, as key contributors to the resolution 
      of inflammation.
FAU - Vago, Juliana P
AU  - Vago JP
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 
      United States.
AD  - Center for Drug Research and Development, Institute of Biological Sciences, 
      Federal University of Minas Gerais, Belo Horizonte, Brazil.
FAU - Sugimoto, Michelle A
AU  - Sugimoto MA
AD  - Center for Drug Research and Development, Institute of Biological Sciences, 
      Federal University of Minas Gerais, Belo Horizonte, Brazil.
AD  - Barts and The London School of Medicine, William Harvey Research Institute, Queen 
      Mary University of London, London, United Kingdom.
FAU - Lima, Katia M
AU  - Lima KM
AD  - Department of Clinical and Toxicological Analyses, School of Pharmacy, Federal 
      University of Minas Gerais, Belo Horizonte, Brazil.
FAU - Negreiros-Lima, Graziele L
AU  - Negreiros-Lima GL
AD  - Department of Clinical and Toxicological Analyses, School of Pharmacy, Federal 
      University of Minas Gerais, Belo Horizonte, Brazil.
FAU - Baik, Nagyung
AU  - Baik N
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 
      United States.
FAU - Teixeira, Mauro M
AU  - Teixeira MM
AD  - Center for Drug Research and Development, Institute of Biological Sciences, 
      Federal University of Minas Gerais, Belo Horizonte, Brazil.
FAU - Perretti, Mauro
AU  - Perretti M
AD  - Barts and The London School of Medicine, William Harvey Research Institute, Queen 
      Mary University of London, London, United Kingdom.
FAU - Parmer, Robert J
AU  - Parmer RJ
AD  - Department of Medicine, Veterans Administration San Diego Healthcare System, 
      University of California, San Diego, San Diego, CA, United States.
FAU - Miles, Lindsey A
AU  - Miles LA
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 
      United States.
FAU - Sousa, Lirlandia P
AU  - Sousa LP
AD  - Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 
      United States.
AD  - Center for Drug Research and Development, Institute of Biological Sciences, 
      Federal University of Minas Gerais, Belo Horizonte, Brazil.
AD  - Department of Clinical and Toxicological Analyses, School of Pharmacy, Federal 
      University of Minas Gerais, Belo Horizonte, Brazil.
LA  - eng
GR  - I01 BX003933/BX/BLRD VA/United States
GR  - R01 HL081046/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190628
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (PLG-R(KT) protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 9001-91-6 (Plasminogen)
SB  - IM
MH  - Animals
MH  - Cell Movement
MH  - Humans
MH  - Macrophages/*immunology
MH  - Male
MH  - Mice, Transgenic
MH  - Neutrophils/immunology
MH  - Phagocytosis
MH  - Phenotype
MH  - Plasminogen/genetics/*immunology
MH  - Pleurisy/*immunology
MH  - Receptors, Cell Surface/genetics/*immunology
PMC - PMC6611080
OTO - NOTNLM
OT  - efferocytosis
OT  - macrophages reprogramming
OT  - plasminogen receptor KT
OT  - plasminogen system
OT  - resolution of inflammation
EDAT- 2019/07/19 06:00
MHDA- 2020/10/22 06:00
PMCR- 2019/01/01
CRDT- 2019/07/19 06:00
PHST- 2019/03/07 00:00 [received]
PHST- 2019/06/10 00:00 [accepted]
PHST- 2019/07/19 06:00 [entrez]
PHST- 2019/07/19 06:00 [pubmed]
PHST- 2020/10/22 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.01458 [doi]
PST - epublish
SO  - Front Immunol. 2019 Jun 28;10:1458. doi: 10.3389/fimmu.2019.01458. eCollection 
      2019.