Ammonia drives dendritic cells into dysfunction.

Journal of immunology (Baltimore, Md. : 1950) (2014-06-27)
Can Luo, Guobo Shen, Ning Liu, Fengming Gong, Xiawei Wei, Shaohua Yao, Dan Liu, Xiu Teng, Ning Ye, Nan Zhang, Xikun Zhou, Jiong Li, Li Yang, Xia Zhao, Li Yang, Rong Xiang, Yu-Quan Wei
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ammonium chloride, for molecular biology, suitable for cell culture, ≥99.5%
Sigma-Aldrich
Ammonium chloride, 99.998% trace metals basis
Sigma-Aldrich
Ammonium chloride, ReagentPlus®, ≥99.5%
Supelco
Ammonium chloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ammonium chloride, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Ammonium chloride, 99.99% trace metals basis
Sigma-Aldrich
Ammonium chloride, puriss., meets analytical specification of Ph. Eur., BP, USP, FCC, 99.5-100.5% (calc. to the dried substance)
Supelco
Ammonium ion solution for ISE, 1000 mg/kg N, analytical standard (for ion-selective electrodes)
Sigma-Aldrich
Ammonium chloride, tested according to Ph. Eur.