Advanced search
1 file | 4.44 MB

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

Author
Organization
Project
10.1152/ajplung.00202.2010
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.
Keywords
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

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 4.44 MB

Citation

Please use this url to cite or link to this publication:

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.
@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},
  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},
}

Altmetric
View in Altmetric
Web of Science
Times cited: