The extracellular matrix of the lung and airway responsiveness in asthma (original) (raw)
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Canadian Journal of Physiology and Pharmacology, 2007
The airway smooth muscle from asthmatic airways produces increased amounts and an altered composition of extracellular matrix proteins. The extracellular matrix can in turn influence the phenotype and function of airway smooth muscle cells, affecting the biochemical, geometric, and mechanical properties of the airway wall. This review provides a brief overview of the current understanding of the biology associated with airway smooth muscle interactions with the extracellular matrix. We present future directions needed for the study of cellular and molecular mechanisms that determine the outcomes of extracellular matrix -airway smooth muscle interactions, and discuss their possible importance as determinants of airway function in asthma.
Respiratory Physiology & Neurobiology, 2009
The impact of genetic factors on asthma is well recognized but poorly understood. We tested the hypothesis that different mouse strains present different lung tissue strip mechanics in a model of chronic allergic asthma and that these mechanical differences may be potentially related to changes of extracellular matrix composition and/or contractile elements in lung parenchyma. Oscillatory mechanics were analysed before and after acetylcholine (ACh) in C57BL/10, BALB/c, and A/J mice, subjected or not to ovalbumin sensitization and challenge. In controls, tissue elastance (E) and resistance (R), collagen and elastic fibres' content, and ␣-actin were higher in A/J compared to BALB/c mice, which, in turn, were more elevated than in C57BL/10. A similar response pattern was observed in ovalbumin-challenged animals irrespective of mouse strain. E and R augmented more in ovalbumin-challenged A/J [E: 22%, R: 18%] than C57BL/10 mice [E: 9.4%, R: 11%] after ACh In conclusion, lung parenchyma remodelled differently yielding distinct in vitro mechanics according to mouse strain.
Tissue and matrix influences on airway smooth muscle function
Pulmonary Pharmacology & Therapeutics, 2009
Asthma is characterized by structural changes in the airways -airway remodelling. These changes include an increase in the bulk of the airway smooth muscle (ASM) and alterations in the profile of extracellular matrix (ECM) proteins in the airway wall. The mechanisms leading to airway remodelling are not well understood. ASM cells have the potential to play a key role in these processes through the production and release of ECM proteins. The ASM cells and ECM proteins are each able to influence the behaviour and characteristics of the other. The modified ECM profile in the asthmatic airway may contribute to the altered behaviour of the ASM cells, such responses to ECM proteins are modulated through the cell surface expression of integrin receptors. ASM cells from asthmatic individuals express different levels of some integrin subunits compared to nonasthmatic ASM cells, which have the potential to further influence their responses to the ECM proteins in the airways. ECM homeostasis requires the presence and activation of matrix metalloproteinases and their tissue inhibitors, which in turn modulate the interaction of the ASM cells and the ECM proteins. Furthermore, the complex interactions of the ASM cells and the ECM in the asthmatic airways and the role played by external stimuli, such as viral infections, to modulate airway remodelling are currently unknown. This review summarises our current understanding of the influence of the ECM on ASM function.
Cells
Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function. In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity. In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression. In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive c...
Journal of Allergy and Clinical Immunology, 2008
Background: Smooth muscle content is increased within the airway wall in patients with asthma and is likely to play a role in airway hyperresponsiveness. However, smooth muscle cells express several contractile and structural proteins, and each of these proteins may influence airway function distinctly. Objective: We examined the expression of contractile and structural proteins of smooth muscle cells, as well as extracellular matrix proteins, in bronchial biopsies of patients with asthma, and related these to lung function, airway hyperresponsiveness, and responses to deep inspiration. Methods: Thirteen patients with asthma (mild persistent, atopic, nonsmoking) participated in this cross-sectional study. FEV 1 % predicted, PC 20 methacholine, and resistance of the respiratory system by the forced oscillation technique during tidal breathing and deep breath were measured. Within 1 week, a bronchoscopy was performed to obtain 6 bronchial biopsies that were immunohistochemically stained for a-SM-actin, desmin, myosin light chain kinase (MLCK), myosin, calponin, vimentin, elastin, type III collagen, and fibronectin. The level of expression was determined by automated densitometry. Results: PC 20 methacholine was inversely related to the expression of a-smooth muscle actin (r 5 20.62), desmin (r 5 20.56), and elastin (r 5 20.78). In addition, FEV 1 % predicted was positively related and deep inspiration-induced bronchodilation inversely related to desmin (r 5 20.60), MLCK (r 5 20.60), and calponin (r 5 20.54) expression. Conclusion: Airway hyperresponsiveness, FEV 1 % predicted, and airway responses to deep inspiration are associated with selective expression of airway smooth muscle proteins and
Altered matrix production in the distal airways of individuals with asthma
Thorax, 2010
Background and aims Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways. Methods Distal and central fibroblasts from controls (n¼12) and patients with mild asthma (n¼11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor b1 (TGFb1). [ 35 S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange chromatography and sodium dodecyl sulfateepolyacrylamide gel electrophoresis. Proliferation was measured with crystal violet, and exhaled nitric oxide was measured by the fractional nitric oxide technique. Results Vesican production from distal fibroblasts was significantly elevated in patients with asthma compared with controls (p<0.001), and the percentage collagenpositive area in distal asthma tissue was also enhanced compared with controls (p<0.01). In addition, distal asthma fibroblasts had reduced proliferation capacity compared with those of controls (by 24%; p<0.01). Furthermore, the alveolar nitric oxide concentration was correlated to distal biglycan and perlecan production of subjects with asthma (r¼À0.857, p<0.05 and r¼À0.750, p<0.05 respectively) Conclusion It is shown that centrally and distally derived fibroblasts differ in their proteoglycan production and proliferation between central and distal tissue, and in those with asthma compared with controls. It is also demonstrated that remodelling is present in distal lung of subjects with mild asthma. This may be of importance in airway remodelling and asthma progression.
Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions
Respiratory Research, 2014
Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix metalloproteinase (TIMP)-3.