دورية أكاديمية
Neutrophil GM-CSF receptor dynamics in acute lung injury.
| العنوان: | Neutrophil GM-CSF receptor dynamics in acute lung injury. |
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| المؤلفون: | De Alessandris S; Department of Medicine, University of Cambridge, Cambridge, United Kingdom., Ferguson GJ; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Dodd AJ; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Juss JK; Department of Medicine, University of Cambridge, Cambridge, United Kingdom., Devaprasad A; Department of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre, Utrecht, Netherlands., Piper S; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Wyatt O; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Killick H; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Corkill DJ; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Cohen ES; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Pandit A; Department of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre, Utrecht, Netherlands., Radstake TRDJ; Department of Rheumatology and Clinical Immunology and Laboratory of Translational Immunology, University Medical Centre, Utrecht, Netherlands., Simmonds R; Department of Medicine, University of Cambridge, Cambridge, United Kingdom., Condliffe AM; Department of Medicine, University of Cambridge, Cambridge, United Kingdom., Sleeman MA; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Cowburn AS; Department of Medicine, University of Cambridge, Cambridge, United Kingdom., Finch DK; Respiratory, Inflammation and Autoimmunity, MedImmune Ltd., Cambridge, United Kingdom., Chilvers ER; Department of Medicine, University of Cambridge, Cambridge, United Kingdom. |
| المصدر: | Journal of leukocyte biology [J Leukoc Biol] 2019 Jun; Vol. 105 (6), pp. 1183-1194. Date of Electronic Publication: 2019 Apr 03. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8405628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-3673 (Electronic) Linking ISSN: 07415400 NLM ISO Abbreviation: J Leukoc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: New York : Alan R. Liss, c1984- |
| مواضيع طبية MeSH: | Acute Lung Injury/*immunology , Gene Expression Regulation/*immunology , Neutrophils/*immunology , Pulmonary Alveoli/*immunology , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/*immunology, Acute Lung Injury/chemically induced ; Acute Lung Injury/genetics ; Acute Lung Injury/pathology ; Adult ; Animals ; Cell Line, Tumor ; Cytokine Receptor Common beta Subunit/genetics ; Cytokine Receptor Common beta Subunit/immunology ; Disease Models, Animal ; Female ; Humans ; Lipopolysaccharides/toxicity ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Neutrophils/pathology ; Pulmonary Alveoli/pathology ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Time Factors |
| مستخلص: | 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. (©2018 The Authors. Society for Leukocyte Biology Published by Wiley Periodicals, Inc.) |
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| معلومات مُعتمدة: | United Kingdom WT_ Wellcome Trust |
| فهرسة مساهمة: | Keywords: LPS; alveolar; apoptosis; inflammation; signaling |
| المشرفين على المادة: | 0 (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) |
| تواريخ الأحداث: | Date Created: 20190404 Date Completed: 20200504 Latest Revision: 20210109 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6850700 |
| DOI: | 10.1002/JLB.3MA0918-347R |
| PMID: | 30942918 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1938-3673 |
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| DOI: | 10.1002/JLB.3MA0918-347R |