Ultrastructure of lung elastin and collagen in mouse models of spontaneous emphysema

O’Donnell, M. D.; O'connor, Clare M.; FitzGerald, M. X.; Lungarella, Giuseppe; Cavarra, Eleonora; Martorana, P. A.

doi:10.1016/s0945-053x(99)00031-1

Cited by 32 publications

(17 citation statements)

References 8 publications

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“…These functional changes have structural origins (21,23,27,28). Tissue destruction in emphysema leads to a spatially heterogeneous structure (29) with variability in airspace sizes (20,21,30,31).…”

Section: Discussionmentioning

confidence: 99%

Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

Takahashi

Majumdar

Parameswaran

et al. 2014

Am J Respir Cell Mol Biol

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Extracellular matrix remodeling and tissue rupture contribute to the progression of emphysema. Lung tissue elasticity is governed by the tensile stiffness of fibers and the compressive stiffness of proteoglycans. It is not known how proteoglycan remodeling affects tissue stability and destruction in emphysema. The objective of this study was to characterize the role of remodeled proteoglycans in alveolar stability and tissue destruction in emphysema. At 30 days after treatment with porcine pancreatic elastase, mouse lung tissue stiffness and alveolar deformation were evaluated under varying tonicity conditions that affect the stiffness of proteoglycans. Proteoglycans were stained and measured in the alveolar walls. Computational models of alveolar stability and rupture incorporating the mechanical properties of fibers and proteoglycans were developed. Although absolute tissue stiffness was only 24% of normal, changes in relative stiffness and alveolar shape distortion due to changes in tonicity were increased in emphysema (P , 0.01 and P , 0.001). Glycosaminoglycan amount per unit alveolar wall length, which is responsible for proteoglycan stiffness, was higher in emphysema (P , 0.001). Versican expression increased in the tissue, but decorin decreased. Our network model predicted that the rate of tissue deterioration locally governed by mechanical forces was reduced when proteoglycan stiffness was increased. Consequently, this general network model explains why increasing proteoglycan deposition protects the alveolar walls from rupture in emphysema. Our results suggest that the loss of proteoglycans observed in human emphysema contributes to disease progression, whereas treatments that promote proteoglycan deposition in the extracellular matrix should slow the progression of emphysema.

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Section: Discussionmentioning

confidence: 99%

Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

Takahashi

Majumdar

Parameswaran

et al. 2014

Am J Respir Cell Mol Biol

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“…Many studies using mouse models of pulmonary emphysema reported changes in the functional mechanical (16,(19)(20)(21), structural (16,(22)(23)(24)(25), or biochemical (9,20,22,(25)(26)(27)(28)(29) properties of the lung. The purpose of the present study was to shed light on the relation among these properties, namely, on structure-function relations.…”

Section: Discussionmentioning

confidence: 99%

Structure–Function Relations in an Elastase-Induced Mouse Model of Emphysema

Hamakawa

Bartolák‐Suki

Parameswaran

et al. 2011

Am J Respir Cell Mol Biol

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Emphysema is a progressive disease characterized by the destruction of peripheral airspaces and subsequent decline in lung function. However, the relation between structure and function during disease progression is not well understood. The objective of this study was to assess the time course of the structural, mechanical, and remodeling properties of the lung in mice after elastolytic injury. At 2, 7, and 21 days after treatment with porcine pancreatic elastase, respiratory impedance, the constituents of lung extracellular matrix, and histological sections of the lung were evaluated. In the control group, no changes were observed in the structural or functional properties, whereas, in the treatment group, the respiratory compliance and its variability significantly increased by Day 21 (P , 0.001), and the difference in parameters decreased with increasing positive end-expiratory pressure. The heterogeneity of airspace structure gradually increased over time. Conversely, the relative amounts of elastin and type I collagen exhibited a peak (P , 0.01) at Day 2, but returned to baseline levels by Day 21. Structure-function relations manifested themselves in strong correlations between compliance parameters and both mean size and heterogeneity of airspace structure (r 2 . 0.9). Similar relations were also obtained in a network model of the parenchyma in which destruction was based on the notion that mechanical forces contribute to alveolar wall rupture. We conclude that, in a mouse model of emphysema, progressive decline in lung function is sensitive to the development of airspace heterogeneity governed by local, mechanical, forceinduced failure of remodeled collagen.

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“…Due to its worldwide impact emphysema has produced immense economic costs for national and international health care infrastructures during the past decades (1)(2)(3)(4)(5)(6)(7)(8)35). Modern lung medicine commonly distinguishes four types of emphysema, which develop in different parts of the respiratory compartment and are moreover characterized by variable intensities with regard to the enzymatic disintegration of the alveolar walls and the associated formation of extremely enlarged air sacs distal to the terminal bronchioles (6)(7)(8)(9)(10).…”

Section: Discussionmentioning

confidence: 99%

“…Emphysema ranks among those chronic lung diseases, which have remarkably attracted medical attention during the past decades (1,2). In general, this insufficiency is characterized by a slowly progressive destruction of the fragile tissues between the lung alveoli and the continuous formation of large peripheral pockets, within which a growing amount of residual air gets trapped.…”

Section: General Aspects With Regard To Emphysemamentioning

confidence: 99%

Theoretical diagnosis of emphysema by aerosol bolus inhalation

Sturm

2017

Ann Transl Med

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Background: The present contribution deals with the theoretical description of aerosol bolus dispersion in lungs being affected by different manifestations of emphysema. The work constructs the hypothesis that each manifestation of emphysema exhibits specific properties with regard to the dispersion of inhaled and exhaled aerosol boluses as well as the deposition of particles from the aerosol pulse.Methods: For an appropriate simulation of single emphysematous manifestations, a previously developed model assuming (I) a random variation of alveolar diameters, (II) an exact localization of diseased structures, and (III) a realistic balance between alveolar air volume and number of air sacs was applied. Dispersion of inhaled and exhaled aerosol boluses was simulated by using the mathematical concept of effective diffusivities. Computations were conducted for an average adult lung (FRC =3,300 mL), symmetric breath-cycles with a length 8 s, and inhalation flow rates of 250 mL/s.Particles used for the model predictions had a uniform diameter of 0.84 µm and a density of 1 g/cm 3 .Results: According to the theoretical data obtained from the model highest aerosol bolus dispersion may be observed in lungs affected by panacinar and bullous emphysema, whereas centriacinar and paraseptal emphysema cause a significant reduction of the phenomenon. Also other statistical parameters exhibit partly remarkable differences among the studied manifestations. Particle deposition in lungs affected by bullous emphysema falls below that of lungs impaired by the other types of emphysema by 2%-50%. Conclusions:From the hypothetical results presented in this study it may be concluded that aerosol bolus inhalation bears a certain potential for the diagnosis of emphysematous structures and, if applied with sufficient accuracy, also for the distinction of single manifestations of emphysema. For a successful use of the technique, however, all statistical bolus parameters and particle deposition have to be subjected to a detailed evaluation.

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Ultrastructure of lung elastin and collagen in mouse models of spontaneous emphysema

Cited by 32 publications

References 8 publications

Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

Structure–Function Relations in an Elastase-Induced Mouse Model of Emphysema

Theoretical diagnosis of emphysema by aerosol bolus inhalation

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