Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany ; These authors contributed equally to this work.
Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
Pulm Circ. 2014 Mar;4(1):128-36. doi: 10.1086/675642.
Our previous findings demonstrated an increase in pulmonary mast cells (MCs) in idiopathic pulmonary arterial hypertension (IPAH). Also, literature suggests a potential role for MCs in chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of lungs from patients is still needed. We systematically investigated the presence/expression of MCs/MC chymase in the lungs of IPAH and COPD patients by (immuno)histochemistry and subsequent quantification. We found that total and perivascular chymase-positive MCs were significantly higher in IPAH patients than in donors. In addition, chymase-positive MCs were located in proximity to regions with prominent expression of big-endothelin-1 in the pulmonary vessels of IPAH patients. Total and perivascular MCs around resistant vessels were augmented and a significant majority of them were degranulated (activated) in COPD patients. While the total chymase-positive MC count tended to increase in COPD patients, the perivascular number was significantly enhanced in all vessel sizes analyzed. Surprisingly, MC and chymase-positive MC numbers positively correlated with better lung function in COPD. Our findings suggest that activated MCs, possibly by releasing chymase, may contribute to pulmonary vascular remodeling in IPAH. Pulmonary MCs/chymase may have compartment-specific (vascular vs. airway) functions in COPD. Future studies should elucidate the mechanisms of MC accumulation and the role of MC chymase in pathologies of these severe lung diseases.
我们之前的研究结果表明，特发性肺动脉高压（IPAH）患者的肺部肥大细胞（MC）数量增加。此外，文献表明 MC 可能在慢性阻塞性肺疾病（COPD）中发挥作用。然而，仍需要对 IPAH 和 COPD 患者的肺部进行全面研究。我们通过（免疫）组织化学和随后的定量分析，系统地研究了 IPAH 和 COPD 患者肺部 MC/MC 糜酶的存在/表达。我们发现，与供体相比，IPAH 患者的总血管周围和阳性 MC 明显更高。此外，在 IPAH 患者的肺血管中，糜酶阳性 MC 位于内皮素-1 表达明显的区域附近。在 COPD 患者中，抗性血管周围的总 MC 和血管周围 MC 增加，并且它们中的大多数处于脱颗粒（激活）状态。虽然 COPD 患者的总阳性 MC 计数有增加的趋势，但所有分析的血管大小的血管周围数量均明显增加。令人惊讶的是，MC 和阳性 MC 数量与 COPD 患者的肺功能改善呈正相关。我们的研究结果表明，活化的 MC 可能通过释放糜酶来促进 IPAH 的肺血管重塑。在 COPD 中，肺 MC/糜酶可能具有特定部位（血管与气道）的功能。未来的研究应阐明 MC 积累的机制以及 MC 糜酶在这些严重肺部疾病中的作用。
