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

Abstract

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/m3 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-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant 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 sidestream 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.

Bilirubin treatment suppresses pulmonary inflammation in a rat model of smoke-induced emphysema

“…We found that the total and indirect bilirubin levels in animals exposed to smoke were significantly lower than in control animals. Emphysema was characterized by increased MLI and MAA, and decreased MAN, infiltration of inflammatory cells and secretion of cytokines such as IL-17, TNF-a, CXCL8, CCL2 and CXCL2 [19,20,27,28]. Bilirubin treatment before exposure to smoke ameliorated the smoke-induced reduction in total and indirect bilirubin and attenuated inflammatory cell recruitment and proinflammatory cytokines secretion, increasing anti-inflammatory cytokine IL-10 levels, and augmenting anti-oxidant SOD activity.…”

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

“…CS was generated from 3R4F Research Cigarettes (Tobacco Research Institute, University of Kentucky, Lexington, KY). Mice were whole body exposed to 100% mainstream CS of 500 mg/m 3 total particulate matter (TPM) for 50 min twice per day for 1, 4, and 6 mo in a manner mimicking natural human smoking habits (24). Control mice were kept in a filtered air (FA) environment, but exposed to the same stress as CS-exposed animals.…”

“…Because of the high toxicity of both its gaseous and particle phases (9,47), CS persistently induces a neutrophil and macrophage inflammatory response in the lower respiratory tract of both humans and animals exposed in experimental models (11,24,49). Whereas the acute reaction during the Ϫ⌬⌬Ct values (⌬⌬Ct ϭ ⌬Cttreated Ϫ ⌬Ctcontrol).…”

Transcellular delivery of vesicular SOCS proteins from macrophages to epithelial cells blunts inflammatory signaling

“…8 B). Typical features of cigarette smoking-associated inflammation are seen in mice after just a few days of cigarette smoke exposure ( John et al, 2014). We exposed C57BL/6 mice to mainstream cigarette smoke from standardized research cigarettes as previously described (Phipps et al, 2010) for 2 h/d for either 3 or 7 d. As compared with smoke-unexposed mice, smoke-exposed mice As demonstrated in BALF from naive mice (Fig.…”