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

作者：John Gerrit; Kohse Katrin; Orasche Juergen; Reda Ahmed; Schnelle Kreis Juergen; Zimmermann Ralf; Schmid Otmar; Eickelberg Oliver; Yildirim Ali Oender^*

来源：Clinical Science, 2014, 126(3-4): 207-221.

DOI：10.1042/CS20130117

• chronic obstructive pulmonary disease (COPD)
• inflammation
• mainstream
• neutrophil
• sidestream
• smoke

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), 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/m(3) TPM (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. BAL (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 (keratinocyte chemoattractant), TNF-alpha (tumour necrosis factor alpha), MIP-2 (macrophage inflammatory protein 2), MIP-1 alpha and MCP-1 (monocyte chennoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestreann exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby determining the outcome of the studies.

• 出版日期2014-2