Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity.
Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity.
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);; 2. Department of Respiratory Medicine, Union Hospital, Tongji Medical College, HUST, Wuhan 430022, PRC;
Yuan
Y
Su
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);
Liping
L
Zhu
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);
Xiangyuan
X
Yu
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);
Lei
L
Cai
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);
Yankai
Y
Lu
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);; 3. Department of Pathology, Union Hospital, Tongji Medical College, HUST, Wuhan 430030, PRC;
Jiwei
J
Zhang
4. Department of Pathology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, PRC;
Tongfei
T
Li
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);; 5. Department of Pathology, Tongji Hospital, Tongji Medical College, HUST, Wuhan 430030, PRC;
Jiansha
J
Li
6. Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine (ZUSM), Hangzhou 310009, PRC;
Jingyan
J
Xia
7. Department of Infectious Diseases, Second Affiliated Hospital, ZUSM, Hangzhou 310009, PRC;
Feng
F
Xu
1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);; 8. Key Laboratory of Molecular Biophysics of the Ministry of Education, HUST, PRC.
Qinghua
Q
Hu
D000818:Animals; D018678:Cholinergic Agents / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D000070634:Non-Neuronal Cholinergic System / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors; D012130:Respiratory Hypersensitivity / Q000628:therapy*
D018678:Cholinergic Agents; D017382:Reactive Oxygen Species; D043587:Receptor, Muscarinic M3
airway hyperresponsiveness; cholinergic hyperactivity; mitochondrial transplantation