Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition

Liesker, Jeroen J W; Hacken, Nick H. T. ten; Zeinstra-Smith, Mieke; Rutgers, S.R.; Postma, Dirkje S.; Timens, Wim

doi:10.2147/copd.s4639

Cited by 39 publications

(24 citation statements)

References 47 publications

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“…Indeed, pulmonary ILC2s are preferentially located in collagen-rich areas close to the airway epithelium (27,29) immediately subjacent to Col VI (63,89,90) that functions as an important anchoring element linked to the basement membrane. Moreover, expression of Col VI is known to be increased during lung fibrosis (63), and subepithelial fibrosis and thickening of the reticular basement membrane have been described as important morphological alterations in CF lungs (91,92). These findings support the pathogenic relevance of the described interplay between accumulated ILC2s, fibroblasts and Col VI for pulmonary tissue remodeling in chronic lung manifestations of CF.…”

Section: Discussionsupporting

confidence: 62%

ILC2 Lung-Homing in Cystic Fibrosis Patients: Functional Involvement of CCR6 and Impact on Respiratory Failure

et al. 2020

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Cystic fibrosis patients suffer from a progressive, often fatal lung disease, which is based on a complex interplay between chronic infections, locally accumulating immune cells and pulmonary tissue remodeling. Although group-2 innate lymphoid cells (ILC2s) act as crucial initiators of lung inflammation, our understanding of their involvement in the pathogenesis of cystic fibrosis remains incomplete. Here we report a marked decrease of circulating CCR6 + ILC2s in the blood of cystic fibrosis patients, which significantly correlated with high disease severity and advanced pulmonary failure, strongly implicating increased ILC2 homing from the peripheral blood to the chronically inflamed lung tissue in cystic fibrosis patients. On a functional level, the CCR6 ligand CCL20 was identified as potent promoter of lung-directed ILC2 migration upon inflammatory conditions in vitro and in vivo using a new humanized mouse model with light-sheet fluorescence microscopic visualization of lung-accumulated human ILC2s. In the lung, blood-derived human ILC2s were able to augment local eosinophil and neutrophil accumulation and induced a marked upregulation of pulmonary type-VI collagen expression. Studies in primary human lung fibroblasts additionally revealed ILC2-derived IL-4 and IL-13 as important mediators of this type-VI collagen-inducing effect. Taken together, the here acquired results suggest that pathologically increased CCL20 levels in cystic fibrosis airways induce CCR6-mediated lung homing of circulating human ILC2s. Subsequent ILC2 activation then triggers local production of type-VI collagen and might thereby drive extracellular matrix remodeling potentially influencing pulmonary tissue destruction in cystic fibrosis patients. Thus, modulating the lung homing capacity of circulating ILC2s and their local effector functions opens new therapeutic avenues for cystic fibrosis treatment.

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Section: Discussionsupporting

confidence: 62%

ILC2 Lung-Homing in Cystic Fibrosis Patients: Functional Involvement of CCR6 and Impact on Respiratory Failure

et al. 2020

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“…Previous studies have been contradictory. One group found thicker Rbm in COPD compared with controls, [ 12 ] with both COPD and control groups in this study being ex-smokers except for 3 COPD subjects who were never smokers. Others have not found this difference [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 54%

Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

et al. 2010

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BackgroundLittle is known about airway remodelling in bronchial biopsies (BB) in smokers and chronic obstructive pulmonary disease (COPD). We conducted an initial pilot study comparing BB from COPD patients with nonsmoking controls. This pilot study suggested the presence of reticular basement membrane (Rbm) fragmentation and altered vessel distribution in COPD.MethodsTo determine whether Rbm fragmentation and altered vessel distribution in BB were specific for COPD we designed a cross-sectional study and stained BB from 19 current smokers and 14 ex-smokers with mild to moderate COPD and compared these to 15 current smokers with normal lung function and 17 healthy and nonsmoking subjects.ResultsThickness of the Rbm was not significantly different between groups; although in COPD this parameter was quite variable. The Rbm showed fragmentation and splitting in both current smoking groups and ex-smoker COPD compared with healthy nonsmokers (p < 0.02); smoking and COPD seemed to have additive effects. Rbm fragmentation correlated with smoking history in COPD but not with age. There were more vessels in the Rbm and fewer vessels in the lamina propria in current smokers compared to healthy nonsmokers (p < 0.05). The number of vessels staining for vascular endothelial growth factor (VEGF) in the Rbm was higher in both current smoker groups and ex-smoker COPD compared to healthy nonsmokers (p < 0.004). In current smoker COPD VEGF vessel staining correlated with FEV1% predicted (r = 0.61, p < 0.02).ConclusionsAirway remodelling in smokers and mild to moderate COPD is associated with fragmentation of the Rbm and altered distribution of vessels in the airway wall. Rbm fragmentation was also present to as great an extent in ex-smokers with COPD. These characteristics may have potential physiological consequences.

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“…Among the general population, asthma accounts for 30-50% of those individuals with fixed airway obstruction (4)(5)(6); in severe or difficult-to-treat adult asthmatics, 55-60% have fixed airway obstruction (7,8). Airway remodeling may explain persistent airflow obstruction present in some asthmatic patients, attributed to goblet cell hyperplasia, decreased epithelial cell and cartilage integrity, subepithelial collagen deposition with increased thickness of the reticular basement membrane, increased airway smooth muscle mass and angiogenesis of the airways (9)(10)(11)(12)(13)(14)(15). This is present in asthmatics with mild disease (16), but tends to worsen in parallel with increasing disease severity (13,17).…”

Section: Epidemiologymentioning

confidence: 99%

Airway Remodeling in Asthma

et al. 2020

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Asthma is an inflammatory disease of the airways that may result from exposure to allergens or other environmental irritants, resulting in bronchoconstriction, wheezing, and shortness of breath. The structural changes of the airways associated with asthma, broadly referred to as airway remodeling, is a pathological feature of chronic asthma that contributes to the clinical manifestations of the disease. Airway remodeling in asthma constitutes cellular and extracellular matrix changes in the large and small airways, epithelial cell apoptosis, airway smooth muscle cell proliferation, and fibroblast activation. These pathological changes in the airway are orchestrated by crosstalk of different cell types within the airway wall and submucosa. Environmental exposures to dust, chemicals, and cigarette smoke can initiate the cascade of pro-inflammatory responses that trigger airway remodeling through paracrine signaling and mechanostimulatory cues that drive airway remodeling. In this review, we explore three integrated and dynamic processes in airway remodeling: (1) initiation by epithelial cells; (2) amplification by immune cells; and (3) mesenchymal effector functions. Furthermore, we explore the role of inflammaging in the dysregulated and persistent inflammatory response that perpetuates airway remodeling in elderly asthmatics.

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Reticular basement membrane in asthma and COPD: Similar thickness, yet different composition

Cited by 39 publications

References 47 publications

ILC2 Lung-Homing in Cystic Fibrosis Patients: Functional Involvement of CCR6 and Impact on Respiratory Failure

ILC2 Lung-Homing in Cystic Fibrosis Patients: Functional Involvement of CCR6 and Impact on Respiratory Failure

Basement membrane and vascular remodelling in smokers and chronic obstructive pulmonary disease: a cross-sectional study

Airway Remodeling in Asthma

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