在异常和遗传性肺动脉高血压中,自然杀手细胞表型和功能受损
Mark L Ormiston1, Chiwen Chang, Lu L Long
1Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Rd., Cambridge, United Kingdom. nwm23@cam.ac.uk
Circulation
|July 27, 2012
概括
自然杀手 (NK) 细胞在肺动脉高血压 (PAH) 中受损,显示功能减弱和变化的子集. 这表明先天免疫在PAH的血管改造和疾病进展中起着关键作用.
科学领域:
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
- 具有天生的免疫力.
背景情况:
- 自然杀手 (NK) 细胞调节血管生成和血管重塑.
- 肺动脉高血压 (PAH) 涉及血管重塑和免疫功能障碍.
- NK细胞在PAH病原发生中的特定作用以前没有被描述.
研究的目的:
- 研究NK细胞在肺动脉高血压 (PAH) 中的作用和功能.
主要方法:
- 在PAH患者中分析NK细胞子集,受体表达 (NKp46,KIRs),细胞因子分泌 (MIP-1β) 和细胞分解功能.
- 评估NK细胞对TGF-β的反应能力.
- 在PAH的动物模型中评估NK细胞功能的评估 (单克罗他林大鼠,缺氧小鼠).
- 对KIR基因多态的基因定型.
主要成果:
- 患有PAH的患者表现出功能缺陷的CD56 (((-) /CD16 (((+) NK细胞的扩张.
- 来自PAH患者的NK细胞显示NKp46和KIR表达减少,MIP-1β分泌减少,细胞毒性受损.
- 来自PAH患者的NK细胞对TGF-β过敏,降低KIRs的调节.
- 在PAH动物模型中,NK细胞数量和细胞毒性降低,在缺氧小鼠中,IFN-γ的产生减少.
- PAH NK细胞产生高的矩阵金属蛋白酶9,这表明它在血管重塑中的作用.
结论:
- 这项研究是第一个确定PAH中NK细胞损伤的研究.
- NK细胞功能障碍在肺动脉高血压的病理生物学中起着重要作用.
- 天生的免疫力与PAH的发展和进展有关.
更多相关视频
相关概念视频
Pulmonary Hypertension: Classification and Pathogenesis
911
Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...
There are various classifications for PH, each relating to different underlying causes and also...
911
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
694
Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
694


