Proteome analysis of multiple compartments in a mouse model of chemical-induced asthma.
Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. Toluene-2,4-diisocyanate (TDI) is one of the most common respiratory sensitizers leading to occupational asthma. Using a mouse model of chemical-induced asthma, we explored proteome changes in multiple compartments of mice sensitized and challenged with TDI or acetone-olive oil (AOO; vehicle). Airway reactivity to methacholine and a bronchoalveolar lavage (BAL) cell count was assessed in treated and control mice, 1 day after challenge. Subsequently, two-dimensional differential gel electrophoresis (2D-DIGE) was performed on auricular lymph nodes, BAL, and serum comparing TDI-treated and vehicle-treated control mice. The differentially expressed proteins were identified by mass spectrometry and pathway analysis was performed. TDI-treated mice exhibit increased airway reactivity (2.6-fold increase) and a neutrophilic inflammation in the BAL fluid, compared to control mice. 2D-DIGE showed 53, 210, and 40 differentially expressed proteins in the auricular lymph nodes, BAL, and serum of TDI-treated versus vehicle-treated mice, respectively. Several of the identified proteins could be linked with inflammation, neutrophil chemotaxis, and/or oxidative stress. Physiologic and immunologic readouts of the asthmatic phenotype, such as inflammation, were confirmed in three compartments by several of the differentially expressed proteins via 2D-DIGE and computerized pathway analysis.
Haenen
Steven
S
Katholieke Universiteit Leuven, Research Unit Lung Toxicology, 3000 Leuven, Belgium.
Vanoirbeek
Jeroen A J
JA
De Vooght
Vanessa
V
Maes
Evelyne
E
Schoofs
Liliane
L
Nemery
Benoit
B
Hoet
Peter H M
PH
Clynen
Elke
E
D000818:Animals; D001249:Asthma / Q000139:chemically induced*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D007249:Inflammation; D013058:Mass Spectrometry; D016210:Methacholine Chloride; D051379:Mice; D009504:Neutrophils; D018384:Oxidative Stress; D020543:Proteome / Q000032:analysis*; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*
D020543:Proteome; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate