Ammonia drives dendritic cells into dysfunction.
J Immunol
; 193(3): 1080-9, 2014 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-24965775
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Cloreto de Amônio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2014
Tipo de documento:
Article