Myofibroblasts are increased in the lung parenchyma in asthma

Abstract

BackgroundIncreased airway smooth muscle is observed in large and small airways in asthma. Semi-quantitative estimates suggest that cells containing alpha smooth muscle actin (α-SMA) are also increased in the lung parenchyma. This study quantified and characterized α-SMA positive cells (α-SMA+) in the lung parenchyma of non-asthmatic and asthmatic individuals.MethodsPost-mortem sections of peripheral lung from cases of fatal asthma (FA), persons with asthma dying of non-respiratory causes (NFA) and non-asthma control subjects (NAC) were stained for α-SMA, quantified using point-counting and normalised to alveolar basement membrane length and interstitial area.Resultsα-SMA+ fractional area was increased in alveolar parenchyma in both FA (14.7 ± 2.8% of tissue area) and NFA (13.0 ± 1.2%), compared with NAC (7.4 ± 2.4%), p < 0.05 The difference was greater in upper lobes compared with lower lobes (p < 0.01) in both asthma groups. Similar changes were observed in alveolar ducts and alveolar walls. The electron microscopic features of the α-SMA+ cells were characteristic of myofibroblasts.ConclusionsWe conclude that in asthma there is a marked increase in α-SMA+ myofibroblasts in the lung parenchyma. The physiologic consequences of this increase are unknown.

TWIST1 DNA methylation is a cell marker of airway and parenchymal lung fibroblasts that are differentially methylated in asthma

“…The larger number of perturbations to DNA methylation in association with asthma in parenchymal fibroblasts versus airway fibroblasts was surprising based on the understanding that the parenchyma’s contribution to the asthmatic phenotype is thought to be minimal. However, airway fibrosis is driven by myofibroblasts (an α smooth muscle actin (αSMA) positive fibroblast subtype), and recently an αSMA-positive fibroblast subtype was identified in the lung parenchyma, with approximately three times more αSMA-positive cells in the parenchyma of individuals with asthma compared to non-asthmatic control subjects [ 21 , 22 ] suggesting that parenchymal-derived fibroblasts in asthmatics may play a role. Furthermore, it has been shown that there is more parenchymal extracellular matrix in asthmatic lungs compared to controls [ 22 ].…”

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

“…αSMA + /COL1 + -coexpressing myofibroblasts are a secretory phenotype of lung stromal mesenchymal cells that are major producers of ECM proteins and matrix metalloproteinases that contribute to lamina reticularis expansion 53,54 , an early and consistent finding in asthma 55,56 . Expanded myofibroblast populations have been observed in acute asthma, fatal severe asthma 57 , refractory asthma 58 , and OVA-sensitized mice 59 . Mesenchymal cell state changes are associated with secretion of paracrine growth factors that expand and sustain the subepithelial myofibroblast population.…”

Pathophysiology of severe asthma: We’ve only just started

“…Reduced lung elastic recoil pressure also explains the reduced lung density on computed tomography (CT) scans, increased small airway collapse and gas trapping during expiration and fixed airway narrowing, all of which are well described in severe asthma . Recently, increased contractile elements have been documented in the lung parenchyma in asthma …”