Immune-mediated inflammation in the pathogenesis of emphysema: insights from mouse models

Abstract

The cellular mechanisms that result in the initiation and progression of emphysema are clearly complex. A growing body of human data combined with discoveries from mouse models utilizing cigarette smoke exposure or protease administration have improved our understanding of emphysema development by implicating specific cell types that may be important for the pathophysiology of COPD. The most important aspects of emphysematous damage appear to be oxidative or protease stress and sustained macrophage activation and infiltration of other immune cells leading to epithelial damage and cell death. Despite the identification of these associated processes and cell types in many experimental studies, the reasons why cigarette smoke and other pollutants result in unremitting damage instead of injury resolution are still uncertain. We propose an important role for macrophages in the sequence of events that lead and maintain this chronic tissue pathologic process in emphysema. This model involves chronic activation of macrophage subtypes that precludes proper healing of the lung. Further elucidation of the cross-talk between epithelial cells that release damage-associated signals and the cellular immune effectors that respond to these cues is a critical step in the development of novel therapeutics that can restore proper lung structure and function to those afflicted with emphysema.

Cigarette smoke directly impairs skeletal muscle function through capillary regression and altered myofibre calcium kinetics in mice

“…These data also differ from studies of skinned diaphragm muscle fibres from COPD patients in which force development and myofilament Ca 2+ sensitivity were diminished (Ottenheijm et al 2005;Stubbings et al 2008). Nonetheless, the mice in the present study did not develop COPD, which was expected within a 2-month CS treatment period (Craig et al 2017), and therefore, impairment in the myofilament Ca 2+ binding function of hindlimb muscles may not be detected early during the progress of COPD.…”

“…2008). Nonetheless, the mice in the present study did not develop COPD, which was expected within a 2‐month CS treatment period (Craig et al . 2017), and therefore, impairment in the myofilament Ca 2+ binding function of hindlimb muscles may not be detected early during the progress of COPD.…”

Impact of emphysema on sputum culture conversion in male patients with pulmonary tuberculosis: a retrospective analysis

“…Time to sputum culture conversion (TCC) was de ned as the number of days between treatment initiation and the rst negative sputum culture and no positive culture thereafter. 7 The delayed conversion may be explained by the high baseline bacillary load. Baseline time to TB detection (TTD) was de ned as time (in days) until MGIT culture showed a positive result at initial sputum culture [6,16].…”

“…Emphysema is a major pathological feature in chronic obstructive pulmonary disease (COPD). The most important aspects of emphysema are sustained oxidative stress and cell damage mediated by macrophages and other cells of the innate and adaptive immune systems, leading to epithelial cell death [7]. Macrophages are localized to sites of alveolar wall destruction in patients with emphysema, and secrete many in ammatory cytokines that contribute to smoking-induced emphysema via elastosis [8].…”

Development, remodeling and regeneration of the lung: coping with the structural and functional challenges of breathing

“…Although considerable research efforts have been undertaken to elucidate the pathogenesis of emphysema, we are still far from a clear and comprehensive understanding of the underlying mechanisms. Craig et al (2017) add a new perspective to this topic by presenting an immunopathological concept of emphysema which focuses on the dysregulation of macrophage-coordinated repair mechanisms in the lung. Moreover, they provide very useful information on the modeling of emphysema in mice.…”