Abstract |
Exposure to acrolein in the ambient air in urban environments represents a considerable hazard to human health. Acrolein exposure causes airway inflammation, accumulation of monocytes, macrophages, and lymphocytes in the interstitium, mucous-cell metaplasia, and airspace enlargement. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subpopulations to pulmonary pathology after exposure to air toxics is unknown. In this study, we used a mouse model of pulmonary pathology induced by repeated acrolein exposure to examine whether pulmonary lymphocyte subpopulations differentially regulate inflammatory-cell accumulation and epithelial-cell pathology. To examine the role of the lymphocyte subpopulations, we used transgenic mice genetically deficient in either alphabeta T cells or gammadelta T cells and measured changes in several cellular, molecular, and pathologic outcomes associated with repeated inhalation exposure to 2.0 ppm or 0.5 ppm acrolein. To examine the potential functions of the lymphocyte subpopulations, we purified these cells from lung tissue of mice repeatedly exposed to 2.0 ppm acrolein, isolated and amplified the messenger RNA ( mRNA*) transcripts, and performed oligonucleotide microarray analysis. Our data demonstrate that alphabeta T cells are primarily responsible for the accumulation of macrophages after acrolein exposure, whereas gammadelta T cells are the primary regulators of epithelial-cell homeostasis after repeated acrolein exposure. These findings are supported by the results of microarray analyses indicating that the two T-cell subpopulations have distinct gene-expression profiles after acrolein exposure. These data provide strong evidence that the T-cell subpopulations in the lung are major determinants of the response to pulmonary toxicant exposure and suggest that it is advantageous to elucidate the effector functions of these cells in the modulation of lung pathophysiology.
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Authors | Michael T Borchers, Scott C Wesselkamper, Hitesh Deshmukh, Erin Beckman, Mario Medvedovic, Maureen Sartor, George D Leikauf, HEI Health Review Committee |
Journal | Research report (Health Effects Institute)
(Res Rep Health Eff Inst)
Issue 146
Pg. 5-29
(Dec 2009)
ISSN: 1041-5505 [Print] United States |
PMID | 20218173
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Air Pollutants
- Receptors, Antigen, T-Cell, alpha-beta
- Receptors, Antigen, T-Cell, gamma-delta
- Acrolein
- Interferon-gamma
- Granulocyte-Macrophage Colony-Stimulating Factor
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Topics |
- Acrolein
(toxicity)
- Air Pollutants
(toxicity)
- Animals
- Apoptosis
(drug effects)
- Bronchoalveolar Lavage Fluid
- Disease Models, Animal
- Female
- Gene Expression
- Granulocyte-Macrophage Colony-Stimulating Factor
(metabolism)
- Interferon-gamma
(metabolism)
- Lung
(drug effects, pathology)
- Macrophages, Alveolar
(drug effects, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Oligonucleotide Array Sequence Analysis
- Pneumonia
(chemically induced, genetics, pathology)
- Receptors, Antigen, T-Cell, alpha-beta
(genetics)
- Receptors, Antigen, T-Cell, gamma-delta
(genetics)
- Respiratory Mucosa
(drug effects, pathology)
- T-Lymphocyte Subsets
(drug effects, physiology)
- Urban Health
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