The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models

Chronic obstructive pulmonary disease (COPD) is caused by exposure to toxic gases and particles, most often cigarette smoke (CS), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations (250 and 500 mg/m3 total particulate matter) of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. Bronchoalveolar lavage fluid was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion (KC, TNF-α, MIP2, MIP-1α, MCP1), proinflammatory gene expression (KC, MIP2, MMP12), and upregulated GM-CSF production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevate...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research