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.

• Authors: El-Bdaoui Haddad, Stephen L Underwood, Dominika Dabrowski, Mark A Birrell, Kerryn McCluskie, Cliff H Battram, Michaela Pecoraro, Martyn L Foster, Maria G Belvisi
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 168 Issue 6 Pg. 3004-16 (Mar 15 2002) ISSN: 0022-1767 [Print] United States
• PMID: 11884473 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Biomarkers
• Cytokines
• Dextrans
• Interleukin-2
• Budesonide
• Cyclosporine
• sephadex
• 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