Time course of cigarette smoke-induced pulmonary inflammation in mice

Abstract

Inflammation of the airways and lung parenchyma plays a major role in the pathogenesis of chronic obstructive pulmonary disease. In the present study a murine model of tobacco smoke-induced emphysema was used to investigate the time course of airway and pulmonary inflammatory response, with a special emphasis on pulmonary dendritic cell (DC) populations.Groups of mice were exposed to either cigarette smoke or to control air for up to 24 weeks. In response to cigarette smoke, inflammatory cells (i.e. neutrophils, macrophages and lymphocytes) progressively accumulated both in the airways and lung parenchyma of mice. Furthermore, a clear infiltration of DCs was observed in airways (10-fold increase) and lung parenchyma (1.5-fold increase) of cigarette-exposed mice at 24 weeks.Flow cytometric analysis of bronchoalveolar lavage (BAL) DCs of smoke-exposed mice showed upregulation of major histocompatability complex II molecules and costimulatory molecules CD40 and CD86, compared with BAL DCs of air-exposed mice. Morphometric analysis of lung histology demonstrated a significant increase in mean linear intercept and alveolar wall destruction after 24 weeks of smoke exposure.In conclusion, the time course of the changes in inflammatory and dendritic cells in both bronchoalveolar lavage and the pulmonary compartment of cigarette smoke-exposed mice was carefully characterised.

Chronic Cigarette Smoke Exposure Primes NK Cell Activation in a Mouse Model of Chronic Obstructive Pulmonary Disease

“…However, a similar priming mechanism may occur following chronic CS exposure, and this would provide a sufficient explanation for our observation that NK cells in both lungs and spleens exhibit signs of priming. The picture is incomplete (48), but several reports have demonstrated that DC activation occurs in COPD patients and in mouse models (49)(50)(51). Maturation of DCs has been correlated with disease severity, strongly suggesting a mechanistic role for DCs in COPD (49).…”

Cigarette smoking alters epithelial apoptosis and immune composition in murine GALT

“…19 Briefly, groups of 10-12 mice were exposed to the tobacco smoke of five cigarettes (Reference Cigarette 3R4F without filter; University of Kentucky, Lexington, KY, USA) four times per day with a 30-min smoke-free interval, 5 days per week for 24 weeks (chronic smoke exposure). An optimal smoke:air ratio of 1:6 was obtained.…”

Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate

“…The chronic inflammatory infiltrate is characterized by augmented numbers of alveolar leukocytes, including both B and T lymphocytes. However, the adaptive immune system may not be essential to the development of pulmonary emphysema in response to chronic tobacco exposure, because emphysema can still be induced in SCID mice, which lack functional lymphocytes (5). This finding indicates that innate inflammatory cells, such as neutrophils and macrophages, may play an essential role in the pathogenesis of COPD.…”

“…Therefore, we examined whether CSE-and nicotine-induced reductions in neutrophil spontaneous death are a result of blockage of Akt deactivation. Akt is recruited to the plasma membrane through specific binding to PtdIns (3,4,5)P3. Only Akt molecules on the plasma membrane can be phosphorylated and activated by two phosphatidylinositoldependent protein kinases (PDKs), thus Akt phosphorylation has been widely used as an indicator of Akt activation.…”

“…We previously established deactivation of the phosphatidylinositol 3,4,5 trisphosphate [PtdIns (3,4,5)P3]/Akt pathway as a causal mediator of neutrophil spontaneous death (12). Akt is a well known cellular survival signal.…”