Cigarette Smoke and DNA Cleavage Promote Lung Inflammation and Emphysema.

: Smoking-related lung diseases are among the most preventable and incurable ailments in the world. Smokers are at increased risk of developing chronic obstructive pulmonary disease that can be further complicated by emphysema and lung cancer. A subset of former smokers shows persistent lung inflammation and progressive loss of lung function, indicating a role for activation of acquired immunity in smoking-induced lung diseases. In addition to the well-established noxious effects of volatile compounds in cigarette smoke, incomplete combustion of tobacco generates nano-sized carbon black (nCB) that accumulate in lung myeloid dendritic cells and macrophages. Experimentally, intra-nasal instillation nCB can cause airway inflammation and emphysema in mice, underscoring their pathogenic role in inflammatory lung diseases. High throughput analyses of macrophages that have engulfed nCB reveal de novo activation of DNA repair enzymes, and histological studies provide evidence for DNA double-stranded breaks. Emphysematous lung myeloid dendritic cells that contain nCB express pro-inflammatory cytokines, and can efficiently differentiate naive CD4 T cells to interferon-g-secreting T helper 1 and interleukin 17A expressing cell subsets. Together these findings indicate that nCB accumulation in lung innate immune cells can initiate and sustain lung inflammation and promote emphysema development.