Neutrophil GM-CSF receptor dynamics in acute lung injury.
Acute Lung Injury
/ chemically induced
Adult
Animals
Cell Line, Tumor
Cytokine Receptor Common beta Subunit
/ genetics
Disease Models, Animal
Female
Gene Expression Regulation
/ immunology
Humans
Lipopolysaccharides
/ toxicity
Male
Mice
Mice, Inbred BALB C
Mice, Transgenic
Neutrophils
/ immunology
Pulmonary Alveoli
/ immunology
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
/ genetics
Time Factors
LPS
alveolar
apoptosis
inflammation
signaling
Journal
Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
14
09
2018
revised:
18
02
2019
accepted:
12
03
2019
pubmed:
4
4
2019
medline:
6
5
2020
entrez:
4
4
2019
Statut:
ppublish
Résumé
GM-CSF is important in regulating acute, persistent neutrophilic inflammation in certain settings, including lung injury. Ligand binding induces rapid internalization of the GM-CSF receptor (GM-CSFRα) complex, a process essential for signaling. Whereas GM-CSF controls many aspects of neutrophil biology, regulation of GM-CSFRα expression is poorly understood, particularly the role of GM-CSFRα in ligand clearance and whether signaling is sustained despite major down-regulation of GM-CSFRα surface expression. We established a quantitative assay of GM-CSFRα surface expression and used this, together with selective anti-GM-CSFR antibodies, to define GM-CSFRα kinetics in human neutrophils, and in murine blood and alveolar neutrophils in a lung injury model. Despite rapid sustained ligand-induced GM-CSFRα loss from the neutrophil surface, which persisted even following ligand removal, pro-survival effects of GM-CSF required ongoing ligand-receptor interaction. Neutrophils recruited to the lungs following LPS challenge showed initially high mGM-CSFRα expression, which along with mGM-CSFRβ declined over 24 hr; this was associated with a transient increase in bronchoalveolar lavage fluid (BALF) mGM-CSF concentration. Treating mice in an LPS challenge model with CAM-3003, an anti-mGM-CSFRα mAb, inhibited inflammatory cell influx into the lung and maintained the level of BALF mGM-CSF. Consistent with neutrophil consumption of GM-CSF, human neutrophils depleted exogenous GM-CSF, independent of protease activity. These data show that loss of membrane GM-CSFRα following GM-CSF exposure does not preclude sustained GM-CSF/GM-CSFRα signaling and that this receptor plays a key role in ligand clearance. Hence neutrophilic activation via GM-CSFR may play an important role in neutrophilic lung inflammation even in the absence of high GM-CSF levels or GM-CSFRα expression.
Identifiants
pubmed: 30942918
doi: 10.1002/JLB.3MA0918-347R
pmc: PMC6850700
doi:
Substances chimiques
Csf2ra protein, mouse
0
Cytokine Receptor Common beta Subunit
0
GM-CSF receptor-alpha subunit, human
0
Lipopolysaccharides
0
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1183-1194Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
©2018 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc.
Références
N Engl J Med. 1992 Jul 2;327(1):28-35
pubmed: 1375975
Am J Respir Crit Care Med. 1997 Dec;156(6):1969-77
pubmed: 9412582
J Leukoc Biol. 2013 Sep;94(3):513-20
pubmed: 23794709
J Leukoc Biol. 2013 Jan;93(1):7-19
pubmed: 22904343
J Exp Med. 2008 Nov 24;205(12):2703-10
pubmed: 18955570
J Thorac Dis. 2014 Nov;6(11):1548-56
pubmed: 25478196
Blood. 1999 Mar 1;93(5):1579-85
pubmed: 10029586
J Infect Dis. 1999 Mar;179 Suppl 2:S342-52
pubmed: 10081506
J Exp Med. 1999 Sep 20;190(6):875-80
pubmed: 10499925
J Clin Invest. 1999 Apr;103(7):1015-21
pubmed: 10194474
Thorax. 2009 Aug;64(8):671-6
pubmed: 19213775
EMBO J. 1994 Nov 1;13(21):5176-85
pubmed: 7957082
Growth Factors. 1988;1(1):41-9
pubmed: 2483336
Crit Care Med. 2012 Jan;40(1):90-7
pubmed: 21926600
Pharm Res. 2015 Jan;32(1):286-99
pubmed: 25208874
J Immunol. 2003 Jun 1;170(11):5359-66
pubmed: 12759409
Am J Respir Cell Mol Biol. 2014 Feb;50(2):253-62
pubmed: 24010952
Am J Respir Crit Care Med. 2016 Oct 15;194(8):961-973
pubmed: 27064380
Am Rev Respir Dis. 1986 Feb;133(2):218-25
pubmed: 3004270
PLoS One. 2012;7(9):e45933
pubmed: 23029326
Am J Respir Cell Mol Biol. 2006 Jun;34(6):766-74
pubmed: 16474098
Blood. 1997 Oct 1;90(7):2772-83
pubmed: 9326245
Am J Respir Cell Mol Biol. 2011 Jun;44(6):879-87
pubmed: 20705940
Thorax. 2018 Oct;73(10):918-925
pubmed: 30064991
Am J Pathol. 1985 Apr;119(1):101-10
pubmed: 2984939
Eur J Immunol. 2004 Jun;34(6):1733-43
pubmed: 15162444
Antiviral Res. 2011 Nov;92(2):319-28
pubmed: 21925209
Am J Respir Crit Care Med. 2010 Nov 15;182(10):1292-304
pubmed: 20622029
Cytokine. 2008 Aug;43(2):114-23
pubmed: 18554923
Int Immunol. 1991 Jun;3(6):571-7
pubmed: 1832294
J Leukoc Biol. 2004 Feb;75(2):358-72
pubmed: 14634056
J Clin Invest. 2001 Dec;108(12):1797-806
pubmed: 11748263
Eur Respir J. 2011 Aug;38(2):285-94
pubmed: 21436349
Lancet Respir Med. 2013 Jul;1(5):395-401
pubmed: 24429204
Blood. 2002 Oct 1;100(7):2607-16
pubmed: 12239175
J Leukoc Biol. 2019 Jun;105(6):1183-1194
pubmed: 30942918