scholarly journals The extracellular matrix of the lung and airway responsiveness in asthma

2016 ◽  
Vol 71 (1) ◽  
Author(s):  
F.G. Salerno ◽  
M.P. Foschino Barbaro ◽  
O. Toungoussova ◽  
E. Carpagnano ◽  
P. Guido ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Mechanical Load ◽  
Bronchial Hyperresponsiveness ◽  
Lung Parenchyma ◽  
Smooth Muscle Contraction ◽  
Airway Remodelling ◽  
Airway Narrowing ◽  
Matrix Deposition ◽  
Airways Smooth Muscle

The extracellular matrix is the main determinant of the structure and of mechanical behaviour of the lung. The extracellular matrix is also responsible for the mechanical interdependence between airway and parenchyma due to the alveolar attachments to the airways. Asthma is characterized by bronchial hyperresponsiveness, airway remodelling and inflammation, and an altered extracellular matrix may play a role in all these functional and structural abnormalities. The excessive airway narrowing observed in asthma may be related to the altered viscoelastic properties of lung parenchyma and airway wall, determining a decrease in the mechanical load opposing the airways’ smooth muscle contraction. Indeed, an altered extracellular matrix deposition in asthma in humans, has been demonstrated. In addition, in the asthmatic lung, the matrix seems to contribute to airway inflammation, airway remodelling, and to those alterations of the smooth muscle function of the airway and morphology typical of asthma.

scholarly journals The mechanics of the lung parenchyma and airway responsiveness to metacholine

2004 ◽  
Vol 61 (4) ◽  
Author(s):  
F.G. Salerno ◽  
O. Resta ◽  
M.P. Foschino-Barbaro ◽  
A. Spanevello
Keyword(s):  
Mechanical Properties ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Muscle Activation ◽  
Mechanical Load ◽  
Lung Parenchyma ◽  
Smooth Muscle Contraction ◽  
Airway Narrowing

The lung parenchyma is anatomically and mechanically connected to the intraparenchymal airways. Due to forces of interdependence the lung parenchyma represents a mechanical load that opposes bronchial narrowing during airway smooth muscle activation. The mechanical load caused by the parenchyma is a function of the number of the alveolar attachments to the airways, and of the mechanical properties of the parenchyma. The extracellular matrix is a major component of the lung parenchyma responsible of most of its mechanical properties. The excessive airway narrowing observed in the asthmatic population may be the consequence of the altered mechanical properties of the extracellular matrix reducing the mechanical load that opposes airway smooth muscle contraction.

scholarly journals Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness

1997 ◽  
Vol 83 (1) ◽  
pp. 140-147 ◽  
Author(s):  
Rodney K. Lambert ◽  
Peter D. Paré
Keyword(s):  
Smooth Muscle ◽  
Shear Modulus ◽  
Airway Remodeling ◽  
Bronchial Hyperresponsiveness ◽  
Lung Parenchyma ◽  
Wall Thickening ◽  
Forced Expiration ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Muscle Shortening

Lambert, Rodney K., and Peter D. Paré. Lung parenchymal shear modulus, airway wall remodeling, and bronchial hyperresponsiveness. J. Appl. Physiol.83(1): 140–147, 1997.—When airways narrow, either through the action of smooth muscle shortening or during forced expiration, the lung parenchyma is locally distorted and provides an increased peribronchial stress that resists the narrowing. Although this interdependence has been well studied, the quantitative significance of airway remodeling to interdependence has not been elucidated. We have used an improved computational model of the bronchial response to smooth muscle agonists to investigate the relationships between airway narrowing (as indicated by airway resistance), parenchymal shear modulus, adventitial thickening, and inner wall thickening at lung recoil pressures of 4, 5, and 8 cmH2O. We have found that, at low recoil pressures, decreases in parenchymal shear modulus have a significant effect that is comparable to that of moderate thickening of the airway wall. At higher lung recoil pressures, the effect is negligible.

Remodelling and Inflammation in Bronchial Asthma

2003 ◽  
Vol 1 (1) ◽  
pp. 9-12 ◽  
Author(s):  
G. Riccioni ◽  
N. D'Orazio ◽  
R. Della Vecchia ◽  
T. Iezzi ◽  
C. Di Ilio
Keyword(s):  
Airway Inflammation ◽  
Bronchial Asthma ◽  
Structural Changes ◽  
Bronchial Hyperresponsiveness ◽  
Lymphocytic Infiltration ◽  
Smooth Muscle Contraction ◽  
Airway Remodelling ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Abnormal Accumulation

Chronic stable asthma is characterized by inflammation of the airway wall, with abnormal accumulation of basophils, eosinophils, lymphocytes, mast cells, macrophages, dendritic cells and myofibroblasts. The airway inflammation is not confined to severe asthma, but is also found in mild and moderate asthma. This inflammation results in a peculiar type of lymphocytic infiltration whereby Th2 lymphocytes secrete cytokines that orchestrate cellular inflammation and promote airway hyperresponsiveness. The term “airway remodelling” in bronchial asthma refers to structural changes that occurr in conjunction with, or because of, chronic airway inflammation. Airway remodelling results in alterations in the airway epithelium, lamina propria, and submucosa, leading to thickening of airway wall. The consequences of airway remodelling in asthma include incompletely reversible airway narrowing, bronchial hyperresponsiveness (BHR), smooth muscle contraction, airway edema, and mucus hypersecretion which may predispose persons with asthma to exacerbations and even death from airway obstruction.

Vascular endothelial growth factor-induced secretion of fibronectin is ERK dependent

2004 ◽  
Vol 286 (3) ◽  
pp. L539-L545 ◽  
Author(s):  
Altaf S. Kazi ◽  
Shidan Lotfi ◽  
Elena A. Goncharova ◽  
Omar Tliba ◽  
Yassine Amrani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Matrix Deposition ◽  
Endothelial Growth Factor

In severe asthma, cytokines and growth factors contribute to the proliferation of smooth muscle cells and blood vessels, and to the increased extracellular matrix deposition that constitutes the process of airway remodeling. Vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, also modulates the function of nonendothelial cell types. In this study, we demonstrate that VEGF induces fibronectin secretion by human airway smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK activation and fibronectin secretion appear to be mediated through the VEGF receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta growth factor. Finally, we demonstrate that ASM cells constitutively secrete VEGF, which is increased in response to PDGF, transforming growth factor-β, IL-1β, and PGE2. We conclude that ASM-derived VEGF, through modulation of the extracellular matrix, may play an important role in airway remodeling seen in asthma.

scholarly journals Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

2002 ◽  
Vol 93 (4) ◽  
pp. 1296-1300 ◽  
Author(s):  
Debra J. Turner ◽  
Peter B. Noble ◽  
Matthew P. Lucas ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Porcine Model ◽  
Smooth Muscle Contraction ◽  
Airway Wall ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

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