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Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
Systemic FasL neutralization increases eosinophilic inflammation in a mouse model of asthma
S K Sharma1, F A Almeida, S Kierstein
1Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, USA.
Allergy
|December 20, 2011
Summary
Fas ligand (FasL) activity helps resolve allergic airway inflammation by regulating T cells and cytokine release. Neutralizing FasL increased eosinophils, indicating its crucial role in controlling allergic responses.
Area of Science:
- Immunology
- Allergic Inflammation Research
Background:
- Eosinophils and lymphocytes are key players in allergic inflammation and susceptible to Fas-mediated apoptosis.
- Fas ligand (FasL) activity is hypothesized to regulate allergic immune responses.
Purpose of the Study:
- To investigate the role of FasL in airway eosinophilia during Aspergillus fumigatus (Af)-induced allergic sensitization.
- To determine if FasL neutralization impacts the inflammatory response in allergic airways.
Main Methods:
- Balb/c mice were sensitized and challenged with Af, with FasL neutralization or control IgG administered.
- FasL expression, bronchoalveolar lavage (BAL) and tissue inflammatory cells, cytokine profiles, and apoptosis were analyzed post-challenge.
Main Results:
- FasL expression peaked with inflammatory cell influx, and soluble FasL preceded inflammation resolution.
- Eosinophil counts negatively correlated with soluble FasL, and FasL neutralization significantly increased eosinophils.
- FasL blockade led to increased T cell activation and pro-eosinophilic cytokine release (IL-5, IL-9, GM-CSF).
Conclusions:
- FasL activity plays a role in resolving allergic airway eosinophilic inflammation.
- FasL regulates T cells and pro-eosinophilic cytokine release during allergic responses.
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