Dept of Exp Medical Science, Lund University, Sweden.
Respir Res. 2011 Oct 20;12(1):139. doi: 10.1186/1465-9921-12-139.
Although mast cells are regarded as important regulators of inflammation and tissue remodelling, their role in cystic fibrosis (CF) and idiopathic pulmonary fibrosis (IPF) has remained less studied. This study investigates the densities and phenotypes of mast cell populations in multiple lung compartments from patients with CF, IPF and never smoking controls.
Small airways, pulmonary vessels, and lung parenchyma were subjected to detailed immunohistochemical analyses using lungs from patients with CF (20 lung regions; 5 patients), IPF (21 regions; 7 patients) and controls (16 regions; 8 subjects). In each compartment the densities and distribution of MCT and MCTC mast cell populations were studied as well as the mast cell expression of IL-6 and TGF-β.
In the alveolar parenchyma in lungs from patients with CF, MCTC numbers increased in areas showing cellular inflammation or fibrosis compared to controls. Apart from an altered balance between MCTC and MCT cells, mast cell in CF lungs showed elevated expression of IL-6. In CF, a decrease in total mast cell numbers was observed in small airways and pulmonary vessels. In patients with IPF, a significantly elevated MCTC density was present in fibrotic areas of the alveolar parenchyma with increased mast cell expression of TGF-β. The total mast cell density was unchanged in small airways and decreased in pulmonary vessels in IPF. Both the density, as well as the percentage, of MCTC correlated positively with the degree of fibrosis. The increased density of MCTC, as well as MCTC expression of TGF-β, correlated negatively with patient lung function.
The present study reveals that altered mast cell populations, with increased numbers of MCTC in diseased alveolar parenchyma, represents a significant component of the histopathology in CF and IPF. The mast cell alterations correlated to the degree of tissue remodelling and to lung function parameters. Further investigations of mast cells in these diseases may open for new therapeutic strategies.
尽管肥大细胞被认为是炎症和组织重塑的重要调节因子，但它们在囊性纤维化（CF）和特发性肺纤维化（IPF）中的作用仍研究较少。本研究调查了 CF、IPF 和从不吸烟对照患者的多个肺区中小气道、肺血管和肺实质中肥大细胞群体的密度和表型。
使用 CF（20 个肺区；5 例患者）、IPF（21 个肺区；7 例患者）和对照（16 个肺区；8 例患者）患者的肺进行详细的免疫组织化学分析。在每个隔室中，研究了 MCT 和 MCTC 肥大细胞群体的密度和分布，以及肥大细胞中 IL-6 和 TGF-β 的表达。
在 CF 患者的肺泡实质中，与对照相比，在显示细胞炎症或纤维化的区域中，MCTC 数量增加。除了 MCTC 和 MCT 细胞之间的平衡改变外，CF 中的肥大细胞还表现出 IL-6 的表达增加。在 CF 中，小气道和肺血管中的总肥大细胞数量减少。在 IPF 患者中，纤维化的肺泡实质区域中 MCTC 密度显著升高，肥大细胞 TGF-β 的表达增加。IPF 中小气道中的总肥大细胞密度不变，肺血管中的肥大细胞密度降低。MCTC 的密度以及 MCTC 的百分比与纤维化程度呈正相关。MCTC 密度的增加以及 MCTC 表达的 TGF-β与患者的肺功能呈负相关。
本研究表明，改变的肥大细胞群体，在患病的肺泡实质中增加了 MCTC 的数量，是 CF 和 IPF 组织病理学的重要组成部分。肥大细胞的改变与组织重塑的程度和肺功能参数相关。进一步研究这些疾病中的肥大细胞可能会开辟新的治疗策略。
Zotero 插件
