Ghent University Academic Bibliography

Advanced

Inflammatory signatures for eosinophilic vs. neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints

Pieter Bogaert UGent, Thomas Naessens UGent, Stefaan De Koker UGent, Benoit Hennuy, Jonathan Hacha, Muriel Smet UGent, Didier Cataldo, Emmanuel Di Valentin, Jacques Piette and Kurt Tournoy UGent, et al. (2011) AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. 300(5). p.L679-L690
abstract
Contrary to the T-helper (Th)-2 bias and eosinophil-dominated bronchial inflammation encountered in most asthmatic subjects, other patients may exhibit neutrophil-predominant asthma subphenotypes, along with Th-1 and Th-17 cells. However, the etiology of many neutrophil-dominated asthma subphenotypes remains ill-understood, in part due to a lack of appropriate experimental models. To better understand the distinct immune-pathological features of eosinophilic vs. neutrophilic asthma types, we developed an ovalbumin (OVA)-based mouse model of neutrophil-dominated allergic pulmonary inflammation. Consequently, we probed for particular inflammatory signatures and checkpoints underlying the immune pathology in this new model, as well as in a conventional, eosinophil-dominated asthma model. Briefly, mice were OVA sensitized using either aluminum hydroxide (alum) or complete Freund's adjuvants, followed by OVA aerosol challenge. T-cell, granulocyte, and inflammatory mediator profiles were determined, along with alveolar macrophage genomewide transcriptome profiling. In contrast to the Th-2-dominated phenotype provoked by alum, OVA/complete Freund's adjuvants adjuvant-based sensitization, followed by allergen challenge, elicited a pulmonary inflammation that was poorly controlled by dexamethasone, and in which Th-1 and Th-17 cells additionally participated. Analysis of the overall pulmonary and alveolar macrophage inflammatory mediator profiles revealed remarkable similarities between both models. Nevertheless, we observed pronounced differences in the IL-12/IFN-gamma axis and its control by IL-18 and IL-18 binding protein, but also in macrophage arachidonic acid metabolism and expression of T-cell instructive ligands. These differential signatures, superimposed onto a generic inflammatory signature, denote distinctive inflammatory checkpoints potentially involved in orchestrating neutrophil-dominated asthma.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
HYPERSENSITIVITY PNEUMONITIS, AIRWAY HYPERRESPONSIVENESS, SEVERE ACUTE ASTHMA, BRONCHOALVEOLAR LAVAGE FLUID, ALVEOLAR MACROPHAGE, MOUSE MODELS, CELLS, DISEASE, LUNG, MATRIX-METALLOPROTEINASE-9, neutrophil-predominant asthma, allergic inflammation, alveolar macrophage, transcriptome, mouse models
journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Am. J. Physiol.-Lung Cell. Mol. Physiol.
volume
300
issue
5
pages
L679 - L690
Web of Science type
Article
Web of Science id
000290088800002
JCR category
RESPIRATORY SYSTEM
JCR impact factor
3.662 (2011)
JCR rank
8/48 (2011)
JCR quartile
1 (2011)
ISSN
1040-0605
DOI
10.1152/ajplung.00202.2010
project
10.1152/ajplung.00202.2010
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1223767
handle
http://hdl.handle.net/1854/LU-1223767
date created
2011-05-14 10:33:30
date last changed
2011-05-16 10:29:53
@article{1223767,
  abstract     = {Contrary to the T-helper (Th)-2 bias and eosinophil-dominated bronchial inflammation encountered in most asthmatic subjects, other patients may exhibit neutrophil-predominant asthma subphenotypes, along with Th-1 and Th-17 cells. However, the etiology of many neutrophil-dominated asthma subphenotypes remains ill-understood, in part due to a lack of appropriate experimental models. To better understand the distinct immune-pathological features of eosinophilic vs. neutrophilic asthma types, we developed an ovalbumin (OVA)-based mouse model of neutrophil-dominated allergic pulmonary inflammation. Consequently, we probed for particular inflammatory signatures and checkpoints underlying the immune pathology in this new model, as well as in a conventional, eosinophil-dominated asthma model. Briefly, mice were OVA sensitized using either aluminum hydroxide (alum) or complete Freund's adjuvants, followed by OVA aerosol challenge. T-cell, granulocyte, and inflammatory mediator profiles were determined, along with alveolar macrophage genomewide transcriptome profiling. In contrast to the Th-2-dominated phenotype provoked by alum, OVA/complete Freund's adjuvants adjuvant-based sensitization, followed by allergen challenge, elicited a pulmonary inflammation that was poorly controlled by dexamethasone, and in which Th-1 and Th-17 cells additionally participated. Analysis of the overall pulmonary and alveolar macrophage inflammatory mediator profiles revealed remarkable similarities between both models. Nevertheless, we observed pronounced differences in the IL-12/IFN-gamma axis and its control by IL-18 and IL-18 binding protein, but also in macrophage arachidonic acid metabolism and expression of T-cell instructive ligands. These differential signatures, superimposed onto a generic inflammatory signature, denote distinctive inflammatory checkpoints potentially involved in orchestrating neutrophil-dominated asthma.},
  author       = {Bogaert, Pieter and Naessens, Thomas and De Koker, Stefaan and Hennuy, Benoit and Hacha, Jonathan and Smet, Muriel and Cataldo, Didier and Di Valentin, Emmanuel and Piette, Jacques and Tournoy, Kurt and Grooten, Johan},
  issn         = {1040-0605},
  journal      = {AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY},
  keyword      = {HYPERSENSITIVITY PNEUMONITIS,AIRWAY HYPERRESPONSIVENESS,SEVERE ACUTE ASTHMA,BRONCHOALVEOLAR LAVAGE FLUID,ALVEOLAR MACROPHAGE,MOUSE MODELS,CELLS,DISEASE,LUNG,MATRIX-METALLOPROTEINASE-9,neutrophil-predominant asthma,allergic inflammation,alveolar macrophage,transcriptome,mouse models},
  language     = {eng},
  number       = {5},
  pages        = {L679--L690},
  title        = {Inflammatory signatures for eosinophilic vs. neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints},
  url          = {http://dx.doi.org/10.1152/ajplung.00202.2010},
  volume       = {300},
  year         = {2011},
}

Chicago
Bogaert, Pieter, Thomas Naessens, Stefaan De Koker, Benoit Hennuy, Jonathan Hacha, Muriel Smet, Didier Cataldo, et al. 2011. “Inflammatory Signatures for Eosinophilic Vs. Neutrophilic Allergic Pulmonary Inflammation Reveal Critical Regulatory Checkpoints.” American Journal of Physiology-lung Cellular and Molecular Physiology 300 (5): L679–L690.
APA
Bogaert, Pieter, Naessens, T., De Koker, S., Hennuy, B., Hacha, J., Smet, M., Cataldo, D., et al. (2011). Inflammatory signatures for eosinophilic vs. neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 300(5), L679–L690.
Vancouver
1.
Bogaert P, Naessens T, De Koker S, Hennuy B, Hacha J, Smet M, et al. Inflammatory signatures for eosinophilic vs. neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. 2011;300(5):L679–L690.
MLA
Bogaert, Pieter, Thomas Naessens, Stefaan De Koker, et al. “Inflammatory Signatures for Eosinophilic Vs. Neutrophilic Allergic Pulmonary Inflammation Reveal Critical Regulatory Checkpoints.” AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY 300.5 (2011): L679–L690. Print.