Chest
Volume 121, Issue 5, Supplement, May 2002, Pages 156S-159S
Journal home page for Chest

Macrophages and the Pathogenesis of COPD

https://doi.org/10.1378/chest.121.5_suppl.156SGet rights and content

Macrophages are long-lived effector cells within the lung. They are reactive, responding to endogenous and exogenous stimuli, as well as proactive, producing mediators that modulate the behavior of surrounding cells. In addition, they play a critical role in the clearance of apoptotic neutrophils. Their role in COPD probably reflects a number of functional properties. However, if the link between increased proteinase burden and tissue destruction and injury in patients with COPD is correct, then macrophages must be very significant. Even though other cells, including epithelial cells and fibroblasts, have been shown to express higher matrix metalloproteinase (MMP) levels in lung tissue from subjects with COPD and emphysema, the numbers of resident cells do not appear to increase by the same factor as that of sequestered macrophages. The combination of a 5- to 10-fold increase in macrophage numbers, the up-regulation of MMPs, and their corelease with other classes of stored proteinases must be highly significant in terms of an increase in proteinase potential in the small airways and respiratory units. This may account for increased tissue destruction and inflammatory mediator activation leading to the pathology that occurs during COPD. Since only about 15% of smokers develop clinically significant disease, it seems likely, in smokers without COPD, that these processes either are strictly controlled or that lung repair mechanisms are more effective.

Section snippets

Macrophages and COPD

Whatever the situation, macrophages are elevated in the lungs of smokers and those patients with COPD, where they accumulate in the alveoli, bronchioli, and small airways. Furthermore, there is a positive association between macrophage numbers in the alveolar walls and the presence of mild-to-moderate emphysema as well as the degree of small airways disease in patients with COPD.1,2 The slow progression and chronicity of COPD parallels the chronic increase of macrophages that is seen at sites

Macrophages and Neutrophils in the Pathogenesis of COPD

Historically, the neutrophil and neutrophil proteinases have been thought to play a major role in the development of emphysema, based on the relationship between α1-antitrypsin deficiency and the predisposition of those affected to develop the disease.3 α1-Antitrypsin (ie, α1-proteinase inhibitor) inhibits neutrophil serine proteinases, especially elastase, and, in turn, neutrophil-derived serine proteinases cleave elastin, the disruption of which may be a significant feature of emphysema.

Proteinases in COPD

If the proteinase hypothesis for the development of emphysema is true, one might hypothesize that the macrophage is responsible.3,7 For > 20 years, studies have demonstrated the release of metalloproteinase activity by macrophages, although the lack of adequate technology long delayed a full understanding of the exact nature of this activity and its contribution to disease processes. More recently, however, a class of proteinases, the MMPs, has been described that accounts for some of the

REFERENCES (21)

There are more references available in the full text version of this article.

Cited by (181)

  • Elastic fibers during aging and disease

    2021, Ageing Research Reviews
    Citation Excerpt :

    The up-regulation of MMP-1, -2, -8, -9, -12, -13 and -14 has been associated mainly with the degradation of collagens and elastin during COPD (Elkington and Friedland, 2006; Lagente et al., 2009). Elastinolytic cysteine proteases such as cathepsin K, L and S have also been hypothesized to be important contributors to COPD (Tetley, 2002). Further, COPD has been described to be associated with systemic consequences such as cardiovascular disease, and it has been postulated that the degradation of elastin in the lungs and arterial wall represents the link between pulmonary and systemic vascular manifestations of COPD (Maclay et al., 2012).

  • Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healthy volunteers and subjects with cystic fibrosis

    2020, Journal of Cystic Fibrosis
    Citation Excerpt :

    In chronic inflammatory conditions of the lung, such as Cystic Fibrosis (CF), neutrophils are abundantly present in the tissue and sputum. Excessive release of neutrophil derived proteolytic enzymes, like neutrophil elastase (NE), will accelerate lung tissue damage, leading to an incapacitating and progressive decline in lung function [1–5]. POL6014 is a novel, potent and selective NE inhibitor.

  • Matrix metalloproteinases in emphysema

    2018, Matrix Biology
    Citation Excerpt :

    Studies to date have largely pointed to specific metalloproteinases made by macrophages, and below we summarize the key findings, discuss uncertainties, and propose new areas for investigation. Macrophages have been long thought to the culprit cells in emphysema [11,12,36,37]. Not only do they produce essentially all of the suspected destructive proteinases, but the number of macrophages is about 10-fold higher in the lungs of smokers than non-smokers and emphysema develops coincident with increased macrophage influx in both human smokers and in several mouse models [38–48].

  • Noncarcinogenic Effects of Cigarette Smoke on the Respiratory Tract

    2018, Comprehensive Toxicology: Third Edition
View all citing articles on Scopus
View full text