Title: Neutrophil and eosinophil granulocytes as key players in a mouse model of chemical-induced asthma
Authors: De Vooght, Vanessa ×
Smulders, Stijn
Haenen, Steven
Belmans, Jochen
Opdenakker, Ghislain
Verbeken, Erik
Nemery, Benoit
Hoet, Peter
Vanoirbeek, Jeroen #
Issue Date: Feb-2013
Publisher: Academic Press
Series Title: Toxicological Sciences vol:131 pages:406-418
Abstract: Diisocyanates are an important cause of chemical-induced occupational asthma. This type of immunologically mediated asthma is often characterized by a predominant granulocytic inflammation in the airways, rather than an infiltration by lymphocytes. We sought to determine the contribution of granulocytes in the outcome of chemical-induced asthma using general and specific leukocyte depletion strategies in an established mouse model of isocyanate asthma. On days 1 and 8, BALB/c mice received dermal applications with toluene-2,4-diisocyanate (TDI) or vehicle (acetone olive oil), followed by two ip injections of cyclophosphamide (CP, days 11 and 13), or one iv injection of antigranulocyte receptor 1 (aGR1, day 13) monoclonal antibody (mAb), or two ip injections of Ly6G-specific mAb (1A8, days 13 and 14). On day 15, the mice were challenged (oropharyngeal administration) with TDI or vehicle. The next day, we assessed methacholine airway hyperreactivity (AHR); bronchoalveolar lavage differential cell count; histopathology and total serum IgE; and auricular lymphocyte subpopulations and release of interleukin (IL)-2, IL-4, IL-10, IL-13, and gamma interferon by these lymphocytes. CP depleted all leukocyte types and completely prevented AHR and airway inflammation. aGR1 depleted granulocytes and CD8(+) lymphocytes, which resulted in a partial prevention in AHR but no decrease in airway inflammation. Depletion of Ly6G-positive granulocytes, i.e., both neutrophils and eosinophils, prevented AHR and lung epithelial damage and significantly reduced airway inflammation. Injection of aGR1 or 1A8 led to significantly changed cytokine release patterns in TDI-treated mice. Granulocytes, both neutrophils and eosinophils, are key cellular players in this model of chemical-induced asthma.
ISSN: 1096-6080
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Occupational, Environmental and Insurance Medicine (-)
Environment and Health - miscellaneous
× corresponding author
# (joint) last author

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