Alrifai Mohammed, Marsh Leigh M, Dicke Tanja, Kılıç Ayse, Conrad Melanie L, Renz Harald, Garn Holger
Institute of Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Medical Faculty, Philipps University Marburg, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Marburg, Germany.
Institute of Laboratory Medicine and Pathobiochemistry - Molecular Diagnostics, Medical Faculty, Philipps University Marburg, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Marburg, Germany ; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
PLoS One. 2014 Jan 21;9(1):e85839. doi: 10.1371/journal.pone.0085839. eCollection 2014.
Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes.
Using BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening.
Chronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued.
Utilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.
过敏性哮喘与慢性气道炎症和进行性气道重塑相关。然而，这些特征发展的动态过程及其自发和药物可逆性仍知之甚少。因此，我们在实验性哮喘模型中研究了气道重塑和修复的动态过程，并研究了药物干预如何影响这些过程。
使用BALB/c小鼠，在有无吸入性糖皮质激素（ICS）治疗的情况下，对慢性哮喘进展和缓解的动力学进行了表征。通过分析支气管肺泡和支气管周围炎性细胞浸润、杯状细胞增生、胶原沉积和平滑肌增厚来评估气道炎症和重塑。
慢性过敏原暴露导致早期（杯状细胞增生）和晚期重塑（胶原沉积和平滑肌增厚）。停止过敏原刺激四周后，嗜酸性粒细胞炎症、杯状细胞增生和胶原沉积得到缓解，仅在八周后观察到淋巴细胞炎症和平滑肌增厚完全消退。在慢性哮喘完全形成之前开始使用ICS治疗，可减少肺部炎症的发展，减少杯状细胞增生和胶原沉积，但不影响平滑肌增厚。即使停止治疗，ICS对气道重塑的这些作用仍可维持四周。
利用实验性哮喘的慢性模型，我们表明反复接触过敏原可诱导小鼠气道发生可逆性重塑和炎症。ICS治疗通过减少气道炎症和重塑，在抑制从急性哮喘向慢性哮喘的转变方面部分有效，但在预防平滑肌肥大方面无效。
