Peikai Huang1, Shushan Wei2, Weihua Huang2, Penghui Wu2, Shuyu Chen3, Ailin Tao3, Hongyu Wang4, Zhenyu Liang5, Rongchang Chen5, Jie Yan6, Qingling Zhang7. 1. Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Department of Respiratory Medicine, Huizhou Municipal Central Hospital, Huizhou, China. 2. Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 3. The Second Affiliated Hospital of Guangzhou Medical University, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China. 4. Firestone Institute for Respiratory Health, The Research Institute of St. Joe's Hamilton, St. Joseph's Healthcare; Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 5. State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 6. The Second Affiliated Hospital of Guangzhou Medical University, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China. Electronic address: jieyan@gzhmu.edu.cn. 7. Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: zqling68@hotmail.com.
Abstract
BACKGROUND: Maintaining an airway clear of bacteria, foreign particles and apoptotic cells by alveolar macrophages is very essential for lung homeostasis. In asthma, the phagocytic capacity of alveolar macrophages is significantly reduced, which is thought to be associated with increased oxidative stress. Hydrogen (H2) has been shown to exert potent antioxidant and anti-inflammatory effects, yet its effects on phagocytosis of alveolar macrophages are unknown. This study is aimed to evaluate the beneficial effects of hydrogen gas inhalation on alveolar macrophage phagocytosis in an ovalbumin (OVA)-induced murine asthma model. METHODS: Female C57BL/6 mice were intraperitoneally sensitized with OVA before they were subject to airway challenge with aerosolized OVA. Hydrogen gas was delivered to the mice through inhalation twice a day (2 h once) for 7 consecutive days. Phagocytic function of alveolar macrophages isolated from bronchoalveolar lavage fluid was assessed by fluorescence-labeled Escherichia coli as well as flow cytometry. RESULTS: Alveolar macrophages isolated from OVA-induced asthmatic mice showed decreased phagocytic capacity to Escherichia coli when compared with those of control mice. Defective phagocytosis in asthmatic mice was reversed by hydrogen gas inhalation. Hydrogen gas inhalation significantly alleviated OVA-induced airway hyperresponsiveness, inflammation and goblet cell hyperplasia, diminished TH2 response and decreased IL-4 as well as IgE levels, reduced malondialdehyde (MDA) production and increased superoxide dismutase (SOD) activity. Concomitantly, hydrogen gas inhalation inhibited NF-κB activation and markedly activated Nrf2 pathway in OVA-induced asthmatic mice. CONCLUSIONS: Our findings demonstrated that hydrogen gas inhalation enhanced alveolar macrophage phagocytosis in OVA-induced asthmatic mice, which may be associated with the antioxidant effects of hydrogen gas and the activation of the Nrf2 pathway.
BACKGROUND: Maintaining an airway clear of bacteria, foreign particles and apoptotic cells by alveolar macrophages is very essential for lung homeostasis. In asthma, the phagocytic capacity of alveolar macrophages is significantly reduced, which is thought to be associated with increased oxidative stress. Hydrogen (H2) has been shown to exert potent antioxidant and anti-inflammatory effects, yet its effects on phagocytosis of alveolar macrophages are unknown. This study is aimed to evaluate the beneficial effects of hydrogen gas inhalation on alveolar macrophage phagocytosis in an ovalbumin (OVA)-induced murine asthma model. METHODS: Female C57BL/6 mice were intraperitoneally sensitized with OVA before they were subject to airway challenge with aerosolized OVA. Hydrogen gas was delivered to the mice through inhalation twice a day (2 h once) for 7 consecutive days. Phagocytic function of alveolar macrophages isolated from bronchoalveolar lavage fluid was assessed by fluorescence-labeled Escherichia coli as well as flow cytometry. RESULTS: Alveolar macrophages isolated from OVA-induced asthmatic mice showed decreased phagocytic capacity to Escherichia coli when compared with those of control mice. Defective phagocytosis in asthmatic mice was reversed by hydrogen gas inhalation. Hydrogen gas inhalation significantly alleviated OVA-induced airway hyperresponsiveness, inflammation and goblet cell hyperplasia, diminished TH2 response and decreased IL-4 as well as IgE levels, reduced malondialdehyde (MDA) production and increased superoxide dismutase (SOD) activity. Concomitantly, hydrogen gas inhalation inhibited NF-κB activation and markedly activated Nrf2 pathway in OVA-induced asthmatic mice. CONCLUSIONS: Our findings demonstrated that hydrogen gas inhalation enhanced alveolar macrophage phagocytosis in OVA-induced asthmatic mice, which may be associated with the antioxidant effects of hydrogen gas and the activation of the Nrf2 pathway.