Experimental Emphysema

Gross, Paul; Pfitzer, Emil A.; Tolker, Ethel B.; Babyak, Mary Ann; Kaschak, Marianne

doi:10.1080/00039896.1965.10664169

Cited by 307 publications

(30 citation statements)

References 4 publications

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“…It should be mentioned that-as shown in animal experiments-inhalative uptake of high concentrations of airborne proteases is associated with emphysematous lesions of the lungs (Gross et al 1964(Gross et al , 1965Palecek et al 1967;Goldring et al 1968;Ackerman et al 1977). Workers highly exposed to papain-containing dust also provided evidence of emphysema (Gandevia and Mitchell 1971).…”

Section: Emphysema Caused By High Air Concentrations Of Proteolytic Ementioning

confidence: 93%

Enzymes as occupational and environmental respiratory sensitisers

Baur

2005

Int Arch Occup Environ Health

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A literature review shows that airborne enzymes occurring in the general environment and in purified form in industrial production have a high allergenic potential to the airways, causing rhinitis, conjunctivitis and asthma. It can be assumed that this also applies to the increasing number of enzymes manufactured by the cloning of fast-growing genetically engineered microorganisms. Cross-sectional studies demonstrate exposure-response relations for IgE-mediated sensitisation and airway disorders. Atopic individuals are more susceptible to enzyme allergy than non-atopic individuals. Skin prick testing and measurement of specific IgE antibodies have been shown to be useful diagnostic tools. Very high concentrations of proteases may lead to emphysema. There is also evidence for non-allergic airway inflammation by proteases, probably via protease-activated receptor-2 and intracellular Ca(2+) release. It is recommended that all enzymes be classified with the risk phrase R42 (may cause sensitisation by inhalation) and that their inhalative uptake be totally avoided.

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Section: Emphysema Caused By High Air Concentrations Of Proteolytic Ementioning

confidence: 93%

Enzymes as occupational and environmental respiratory sensitisers

Baur

2005

Int Arch Occup Environ Health

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“…Ineffective repair of elastin and other ECM components results in air space enlargement that defines pulmonary emphysema. This ‘proteinase/antiproteinase imbalance’ hypothesis was first proposed 40 years ago, based on the observations that smokers with a deficiency of α 1 -antitrypsin were at increased risk for pulmonary emphysema [9], and that intratracheal administration of papain (a plant proteinase) resulted in emphysema in experimental animals [10]. Later, it was described that instillation of neutrophil elastase causes pulmonary emphysema in animal experiments [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Matrix Metalloproteinase-12 and Cathepsin D Expression in Pulmonary Macrophages and Dendritic Cells of Cigarette Smoke-Exposed Mice

Bracke

Cataldo

Maes

et al. 2005

Int Arch Allergy Immunol

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An imbalance between proteinases and their inhibitors is believed to play an essential role in the development of chronic obstructive pulmonary disease (COPD) and pulmonary emphysema. COPD is mainly caused by cigarette smoking, and is characterized by an increase in inflammatory cells in small airways and lung parenchyma. We examined the mRNA expression of several proteinases in lungs of mice exposed to cigarette smoke or control air. After 1, 3 and 6 months’ smoke exposure there was a significant increase of matrix metalloproteinase (MMP)-12 and Cathepsin D mRNA, compared to air-exposed mice. To determine the cellular origin of MMP-12 and Cathepsin D, we isolated dendritic cells (DCs) and macrophages from the lungs of mice. There was an increase in MMP-12 mRNA after smoke exposure in both macrophage and DC populations, whereas Cathepsin D was predominantly expressed in macrophages. Immunohistochemistry clearly revealed the expression of Cathepsin D protein in alveolar macrophages of cigarette smoke-exposed mice, in contrast to air-exposed littermates. Western blots on lung tissue demonstrated an increase of MMP-12 protein in cigarette smoke-exposed animals. These results indicate that cigarette smoke increases the expression of MMP-12 and Cathepsin D in the lungs of mice, and that not only macrophages but also DCs produce MMP-12.

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“…Destruction of lung elastin in experimental animals by purified elastase can reproduce the histological and mechanical features of emphysema (1)(2)(3)(4)(5). Although alveolar macrophages are the major inflammatory cell in the histopathology of smoking individuals, neutrophils are currently considered the major source of elastase activity likely to lead to disruption of elastin and progressive emphysema.…”

Section: Introductionmentioning

confidence: 99%

Comparison of live human neutrophil and alveolar macrophage elastolytic activity in vitro. Relative resistance of macrophage elastolytic activity to serum and alveolar proteinase inhibitors.

Chapman¹,

Stone²

1984

J. Clin. Invest.

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Again in serum-free media, neutrophils degraded eightfold more elastin than macrophages but only macrophages degraded sepharose-coupled elastin in the presence of 10% serum. Because of these findings, we compared the enzymatic mechanisms of elastin breakdown by macrophages with that of neutrophils. Macrophage elastolytic activity is largely (65-80%) due to a cysteine proteinase(s), at least part of which is Cathepsin B. Approximately half of the cysteine proteinase activity appeared to be expressed at or near the cell surface.

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Experimental Emphysema

Cited by 307 publications

References 4 publications

Enzymes as occupational and environmental respiratory sensitisers

Enzymes as occupational and environmental respiratory sensitisers

Matrix Metalloproteinase-12 and Cathepsin D Expression in Pulmonary Macrophages and Dendritic Cells of Cigarette Smoke-Exposed Mice

Comparison of live human neutrophil and alveolar macrophage elastolytic activity in vitro. Relative resistance of macrophage elastolytic activity to serum and alveolar proteinase inhibitors.

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