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Critical role for T cells in Sephadex-induced airway inflammation: pharmacological and immunological characterization and molecular biomarker identification.

Abstract
Intratracheal instillation of Sephadex particles is a convenient model for assessing the impact of potential anti-inflammatory compounds on lung eosinophilia thought to be a key feature in asthma pathophysiology. However, the underlying cellular and molecular mechanisms involved are poorly understood. We have studied the time course of Sephadex-induced lung eosinophilia, changes in pulmonary T cell numbers, and gene and protein expression as well as the immunological and pharmacological modulation of these inflammatory indices in the Sprague Dawley rat. Sephadex increased T cell numbers (including CD4(+) T cells) and evoked a pulmonary eosinophilia that was associated with an increase in gene/protein expression of the Th2-type cytokines IL-4, IL-5, and IL-13 and eotaxin in lung tissue. Sephadex instillation also induced airway hyperreactivity to acetylcholine and bradykinin. A neutralizing Ab (R73) against the alphabeta-TCR caused 54% depletion of total (CD2(+)) pulmonary T cells accompanied by a significant inhibition of IL-4, IL-13 and eotaxin gene expression together with suppression (65% inhibition) of eosinophils in lung tissue 24 h after Sephadex treatment. Sephadex-induced eosinophilia and Th2 cytokine gene and/or protein expression were sensitive to cyclosporin A and budesonide, compounds that inhibit T cell function, suggesting a pivotal role for T cells in orchestrating Sephadex-induced inflammation in this model.
AuthorsEl-Bdaoui Haddad, Stephen L Underwood, Dominika Dabrowski, Mark A Birrell, Kerryn McCluskie, Cliff H Battram, Michaela Pecoraro, Martyn L Foster, Maria G Belvisi
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 6 Pg. 3004-16 (Mar 15 2002) ISSN: 0022-1767 [Print] United States
PMID11884473 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Biomarkers
  • Cytokines
  • Interleukin-2
  • Budesonide
  • Cyclosporine
  • sephadex
  • Dextrans
  • Acetylcholine
  • Bradykinin
Topics
  • Acetylcholine (administration & dosage)
  • Animals
  • Antibodies, Monoclonal (administration & dosage)
  • Biomarkers (analysis)
  • Bradykinin (administration & dosage)
  • Bronchial Hyperreactivity (chemically induced)
  • Budesonide (therapeutic use)
  • Cell Movement (drug effects, immunology)
  • Cells, Cultured (drug effects, immunology, metabolism)
  • Cyclosporine (therapeutic use)
  • Cytokines (biosynthesis, genetics)
  • Dextrans (toxicity)
  • Gene Expression Regulation (drug effects, immunology)
  • Inflammation (chemically induced, drug therapy, immunology, metabolism)
  • Interleukin-2 (biosynthesis)
  • Intubation, Intratracheal
  • Lung (drug effects, immunology, metabolism, pathology)
  • Lymphocyte Depletion
  • Male
  • Mast Cells (drug effects, immunology)
  • Pulmonary Eosinophilia (chemically induced, immunology)
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocyte Subsets (drug effects, immunology, metabolism)
  • Time Factors

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