Molecular pathogenesis of emphysema

Abstract

Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema.

Targeting the phospholipase A2 receptor ameliorates premature aging phenotypes

“…Our results point out that bisphosphonate strongly impacts senescent phenotype reinforcing a potential functional link between bone fragility during aging and increase cellular senescence. It has also been reported that bisphosphonates can impact bone‐independent marks of aging like emphysema (Ueno et al, 2015), emphysema being thought to be regulated by cellular senescence (Taraseviciene‐Stewart, & Voelkel, 2008), further suggesting that FDPS/bisphosphonates can regulate cellular senescence and aging beyond their well‐known bone effects.…”

Elimination of p19ARF‐expressing cells protects against pulmonary emphysema in mice

“…In addition to emphysema, COPD is frequently associated with an increased number of alveolar inflammatory cells (Taraseviciene‐Stewart & Voelkel, 2008), and PPE‐induced emphysema also causes alveolar inflammation (Houghton et al, 2006). In the PPE‐induced emphysema model, elastin fragments produced by PPE increase macrophage numbers, which secrete elastolytic enzymes such as MMPs (Houghton et al, 2006; Hunninghake et al, 1981).…”

Pulmonary Epithelial Neuropilin-1 Deletion Enhances Development of Cigarette Smoke–induced Emphysema

“…Because mounting evidence suggests that the apoptotic machinery is also necessary to generate an emphysema phenotype (64,(67)(68)(69), an alternative and potentially complementary hypothesis to explain host susceptibility to the injurious effects of chronic smoke exposure has evolved. This hypothesis suggests that CS-induced alveolar destruction could be exacerbated by abnormalities in pathways critical for lung development and postnatal lung homeostasis, creating an imbalance between cellular programs regulating lung injury and repair (69,70).…”

“…This hypothesis suggests that CS-induced alveolar destruction could be exacerbated by abnormalities in pathways critical for lung development and postnatal lung homeostasis, creating an imbalance between cellular programs regulating lung injury and repair (69,70). Several lines of investigation have supported a role for the disruption of alveolar structural maintenance in the pathogenesis of emphysema.…”