title: Ammonia drives dendritic cells into dysfunction.
abstract: Ammonia levels are often elevated in patients with cirrhosis or tumors. Patients with these diseases are immunocompromised. In this study, we investigated the effects of ammonia on a member of the immune cell family, the dendritic cells (DCs). Our results demonstrated that ammonia diminished cell count, phagocytosis, and lymphocyte stimulation of DCs. Ammonia also induced DC swelling, excessive reactive oxygen species production, and mitochondrial damage, which may constitute the underlying mechanism of ammonia-induced DC dysfunction. In ammonium chloride (NH4Cl)-loaded mice, DCs exhibited lowered phagocytosis and a weakened immune response to the chicken OVA vaccine. DCs from patients with cirrhosis or ammonia-treated healthy human blood both exhibited diminished phagocytosis. Moreover, tumor cell conditioned medium drove DCs into dysfunction, which could be reversed by ammonia elimination. In a murine colon carcinoma model, we found that ammonia could regulate tumor growth involving DCs and their related immune response. These findings reveal that ammonia could drive DCs into dysfunction, which contributes to the immunocompromised state of patients with cirrhosis or tumors.
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Can
authors: C
authors: Luo
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Guobo
authors: G
authors: Shen
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Ning
authors: N
authors: Liu
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Fengming
authors: F
authors: Gong
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China; yqwei@vip.sina.com.
authors: Xiawei
authors: X
authors: Wei
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Shaohua
authors: S
authors: Yao
authors: Department of Respiratory Medicine, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Dan
authors: D
authors: Liu
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Xiu
authors: X
authors: Teng
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Ning
authors: N
authors: Ye
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Nan
authors: N
authors: Zhang
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Xikun
authors: X
authors: Zhou
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Jiong
authors: J
authors: Li
authors: Division of Digestive Diseases, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Li
authors: L
authors: Yang
authors: Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Sichuan 610041, People's Republic of China; and.
authors: Xia
authors: X
authors: Zhao
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China;
authors: Li
authors: L
authors: Yang
authors: Department of Immunology, Nankai University School of Medicine, Tianjin 300071, People's Republic of China.
authors: Rong
authors: R
authors: Xiang
authors: State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Sichuan 610041, People's Republic of China; yqwei@vip.sina.com.
authors: Yu-Quan
authors: YQ
authors: Wei
mesh_terms: D000643:Ammonium Chloride / Q000633:toxicity*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D002452:Cell Count; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects / Q000648:ultrastructure; D000083162:Mitochondrial Permeability Transition Pore; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D061251:Primary Cell Culture
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000643:Ammonium Chloride