Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 170, Issue 2, Pages 126-132Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200311-1499OC
Keywords
toll-like receptor; innate immunity; endotoxin; ozone; residual oil fly ash
Categories
Funding
- NHLBI NIH HHS [HL07538, HL074518, HL66611, HL66604, HL62641] Funding Source: Medline
- NIEHS NIH HHS [ES012496, ES00703, ES012717, ES11375, ES07498, ES7031] Funding Source: Medline
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Inhalation of toxins commonly found in air pollution contributes to the development and progression of asthma and environmental airway injury. In this study, we investigated the requirement of toll-like receptor 4 (TLR4) in mice for pulmonary responses to three environmental toxins: aerosolized lipopolysaccharide, particulate matter (residual oil fly ash), and ozone. The physiologic and biologic responses to these toxins were evaluated by the extent of airway responsiveness, neutrophil recruitment to the lower respiratory tract, changes in inflammatory cytokines, and the concentration of protein in the lavage fluid. Genetically engineered, TLR4-deficient mice (C57BL/6(TLR4-/-)) were unresponsive to inhaled lipopolysaccharide, except for minimal increases in some inflammatory cytokines. In contrast, C57BL/6(TLR4-/-) mice did not differ from wild-type mice in their airway response to instilled residual oil fly ash or acute ozone exposure; however, we found that, despite a robust inflammatory response, C57BL/6(TLR4-/-) mice are protected against the development of airway hyperresponsiveness after subchronic ozone exposure. These data demonstrate in the mouse that the requirement of TLR4 for pulmonary inflammation depends on the nature of the toxin and appears specific to toxin and exposure conditions.
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