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http://purl.uniprot.org/citations/30942918http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30942918http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.org/dc/terms/identifier"doi:10.1002/jlb.3ma0918-347r"xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Sleeman M.A."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Pandit A."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Chilvers E.R."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Condliffe A.M."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Juss J.K."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Cohen E.S."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Finch D.K."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Ferguson G.J."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Simmonds R."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Wyatt O."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Piper S."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Cowburn A.S."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Corkill D.J."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Radstake T.R.D.J."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"De Alessandris S."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Devaprasad A."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Dodd A.J."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/author"Killick H."xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/name"J Leukoc Biol"xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/pages"1183-1194"xsd:string
http://purl.uniprot.org/citations/30942918http://purl.uniprot.org/core/title"Neutrophil GM-CSF receptor dynamics in acute lung injury."xsd:string