| Title | Immunological determinants of ventilatory changes induced in mice by dermal sensitization and respiratory challenge with toluene diisocyanate. | | Author(s) | Tarkowski M, Vanoirbeek JA, Vanhooren HM, De Vooght V, Mercier CM, Ceuppens J, Nemery B, Hoet PH | | Institution | Laboratory of Pneumology, unit Lung toxicology, K.U.Leuven, Leuven, Belgium; Department of Immunotoxicology, Nofer Institute of Occupational Medicine, Lodz, Poland. | | Source | Am J Physiol Lung Cell Mol Physiol 2006 Sep 8. | | Abstract | The objective of the study was to characterize better the immunological mechanisms underlying a previously developed animal model of chemical-induced asthma. BALB/c and SCID mice received toluene diisocyanate (TDI) or vehicle on each ear, on day 1 and/or 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: Penh and actual resistance (R) measurements. Pulmonary inflammation was assessed 1, 6 and 24 h after challenge by broncho-alveolar lavage (BAL). TNF-alpha and MIP-2 levels were measured in BAL. Immunological parameters included total IgE, IgG1 and IgG2a in serum, lymphocyte populations in auricular 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 concanavaline 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 that it is not characterized by a preferential stimulation of Th1 or Th2 lymphocytes. Key words: occupational asthma, T-lymphocytes subtypes, murine model, Severe Combined Immunodeficiency Disease (SCID) mice, toluene diisocyanate. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 16963530 |
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