title: Proteome analysis of multiple compartments in a mouse model of chemical-induced asthma.
abstract: 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.
authors.affiliation: Katholieke Universiteit Leuven, Research Unit Lung Toxicology, 3000 Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Haenen
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Vanoirbeek
authors.forename: Vanessa
authors.initials: V
authors.lastname: De Vooght
authors.forename: Evelyne
authors.initials: E
authors.lastname: Maes
authors.forename: Liliane
authors.initials: L
authors.lastname: Schoofs
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
authors.forename: Elke
authors.initials: E
authors.lastname: Clynen
mesh_terms: 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*
chemical_list: D020543:Proteome; D016210:Methacholine Chloride; D014051:Toluene 2,4-Diisocyanate