Complement System in Alcohol-Associated Liver Disease

Autor(es)

Santiesteban-Lores, Lazara Elena ^[1] ; Carneiro, Milena Carvalho ^[1] ; Isaac, Lourdes ^[1] ; Bavia, Lorena ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Immunology Letters; v. 236, p. 37-50, AUG 2021.
• Citações Web of Science: 0

Resumo

Innate immunity contributes effectively to the development of Alcohol-Associated liver disease (ALD). Particularly, human studies and murine models of ALD have shown that Complement activation plays an important role during the initial and later stages of ALD. The Complement System may contribute to the pathogenesis of this disease since it has been shown that ethanol-derived metabolic products activate the Complement cascade on liver membranes, leading to hepatocellular damage. However, studies evaluating the plasma levels of Complement proteins in ALD patients present contradictory results in some cases, and do not establish a well-marked role for each Complement component. The impairment of leukocyte chemoattractant activity observed in these patients may contribute to the susceptibility to bacterial infections in the latter stages of the disease. On the other hand, murine models of ALD have provided more detailed insights into the mechanisms that link the Complement System to the pathogenesis of the disease. It has been observed that Classical pathway can be activated via C1q binding to apoptotic cells in the liver and contributes to the development of hepatic inflammation. C3 contributes to the accumulation of triglycerides in the liver and in adipose tissue, while C5 seems to be involved with inflammation and liver injury after chronic ethanol consumption. In this review, we present a compendium of studies evaluating the role of Complement in human and murine models of ALD. We also discuss potential therapies to human ALD, highlighting the use of Complement inhibitors. (AU)

• Processo FAPESP: 17/12924-3 - Etiopatogênese da Leptospirose: contribuição do sistema complemento in vivo e in vitro para o controle da infecção e desencadeamento da resposta inflamatória tecidual: estudo de polimorfismos de genes do sistema complemento em pacientes com Leptospirose
• Beneficiário: Lourdes Isaac
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/19800-3 - Treinamento em técnicas de microbiologia e imunologia
• Beneficiário: Milena Carvalho Carneiro
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 07/03393-2 - Expressão gênica dependente do componente C5 em fígado de camundongos com lesão hepática induzida por etanol
• Beneficiário: Lorena Bavia
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto