Chronic obstructive pulmonary disease: molecular and cellularmechanisms

Abstract

Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective.There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases.The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease. Eur Respir J 2003; 22: 672-688.

Native matrix-based human lung alveolar tissue model in vitro: studies of the reparatory actions of mesenchymal stem cells

“…MMP-9, and their up-regulation reflects similar tendencies reported by other authors (Braber et al 2011;Overbeek et al 2013). In general, expression of MMPs in lung tissue is described as a characteristic of tissue remodeling associated with various biological processes, such as development, inflammation, migration of cells, wound repair and other (Legrand et al 1999;Itoh et al 2002;Barnes et al 2003;Wolf et al 2003;Greenlee et al 2007;Crosby and Waters 2010). Secretion of pro-inflammatory chemokine GROa was increased by CSE in our native matrix model in contrast to some other reports (Victoni et al 2014) suggesting that study model and matrix origin might be important.…”

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

“…However, changes in NOX expression or activation during conditions of acute or chronic lung disease are also suggestive of a potential contributing role for NOX in disease pathology. Indeed, it is well appreciated that chronic diseases of the respiratory tract, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, or various forms of lung cancer, are associated with increased oxidative stress and enhanced ROS production (194)(195)(196)(197), which may largely originate from enhanced and/or inappropriate NOX activation. To explain this paradox of beneficial and potentially detrimental effects of NOX enzymes, Lambeth recently proposed that NOX enzymes represent an example of antagonistic pleiotropy, meaning that potentially harmful genes are retained during evolution because they confer a reproductive advantage during early stages of life (198).…”

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

“…The pathogenesis involves chronic airway inflammation, associated with an infiltration of inflammatory cells (macrophages and neutrophils), oxidative stress, parenchymal destruction, recurrent infection and imbalance between proteases and antiproteases activity where an excess of proteolytic enzymes (MMPs, cysteine and serine proteinases) is not counterbalanced by a similar rise of antiproteolytic compounds [10][11][12][13]. COPD embraces two separate chronic lung diseases: pulmonary emphysema and chronic bronchitis.…”