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Am J Physiol Lung Cell Mol Physiol 292: L207-L214, 2007. First published September 8, 2006; doi:10.1152/ajplung.00157.2005
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Immunological determinants of ventilatory changes induced in mice by dermal sensitization and respiratory challenge with toluene diisocyanate

Maciej Tarkowski,1,2,* Jeroen A. J. Vanoirbeek,1,* Hadewijch M. Vanhooren,1 Vanessa De Vooght,1 Caroline M. Mercier,1 Jan Ceuppens,3 Benoit Nemery,1 and Peter H. M. Hoet1

1Laboratory of Lung Toxicology, Katholieke Universiteit Leuven, Leuven, Belgium; 2Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Lodz, Poland; and 3Laboratory of Clinical Immunology, Katholieke Universiteit Leuven, Leuven, Belgium

Submitted 7 April 2005 ; accepted in final form 6 September 2006

The objective of the study was to characterize better the immunologic mechanisms underlying a previously developed animal model of chemical-induced asthma. BALB/c and severe combined immunodeficiency disease (SCID) mice received toluene diisocyanate (TDI) or vehicle on each ear on day 1 and/or day 7. On day 10, they were intranasally challenged with TDI or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after challenge. Reactivity to methacholine was measured 23 h later: enhanced pause and actual resistance measurements. Pulmonary inflammation was assessed 1, 6, and 24 h after challenge by bronchoalveolar lavage (BAL). Tumor necrosis factor-{alpha} and macrophage inflammatory protein (MIP)-2 levels were measured in BAL. Immunological parameters included total IgE, IgG1, and IgG2a in serum, lymphocyte populations in auricular and cervical lymph nodes, and IL-4 and IFN-{gamma} levels in supernatants of lymph node cells, cultured with or without concanavalin A. Ventilatory changes suggestive of airway obstruction and increased methacholine reactivity were observed in all TDI-sensitized and TDI intranasally instilled mice, except in SCID mice. A neutrophil influx, accompanied by an increase in MIP-2 levels, was found in BAL of all responding groups 6 and 24 h after intranasal challenge. In BALB/c mice an increased level of CD19+ B cells was found in the auricular lymph nodes. IL-4 and IFN-{gamma} levels were increased in supernatants of concanavalin A-stimulated auricular lymph node cells from BALB/c mice completely treated with TDI. These results indicate that our model is dependent on the presence of lymphocytes, but it is not characterized by a preferential stimulation of Th1 or Th2 lymphocytes.

occupational asthma; severe combined immunodeficiency disease mice; murine model; T lymphocyte subtypes



Address for reprint requests and other correspondence: B. Nemery, Laboratory of Lung Toxicology, Katholieke Universiteit Leuven, Herestraat 49 bus 706, 3000 Leuven, Belgium (e-mail: ben.nemery{at}med.kuleuven.be)




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