Mannan-binding lectin deficiency exacerbates sterile liver injury in mice through enhancing hepatic neutrophil recruitment

• DOI: 10.1002/jlb.3a0718-251r
• Publication Date: 2018-10-24T00:52:51Z
• Authors: Jia Zhou; Junru Li; Yu Yu; Yan Liu; Huifang Li; Yunzhi Liu; Jun Wang; Liyun Zhang; Xiao Lu; Zhengliang Chen; Daming Zuo
• Keywords: Mice, Inbred C57BL; 0301 basic medicine; 03 medical and health sciences; Liver; Neutrophil Infiltration; Macrophages; Chemokine CXCL2; Animals; Dependovirus; Carbon Tetrachloride; Mannose-Binding Lectin; 3. Good health

Abstract Noninfectious liver injury, including the effects of drugs and diet, is a major cause diseases worldwide. The innate inflammatory response to hepatocyte death plays crucial role in outcome injury. Mannan-binding lectin (MBL) pattern recognition molecule immune system, which primarily produced by liver. MBL deficiency occurs with high frequency population reported associated predisposition infectious diseases. We here observed that genetic ablation strongly sensitizes mice sterile injury induced carbon tetrachloride (CCl4). Aggravated damage was shown CCl4-administrated MBL−/− mice, as evidenced severe death, elevated serum alanine aminotransferase lactate dehydrogenase activity, enhanced production cytokines. Mechanistic studies established caused increased chemokine CXCL2 from macrophages upon CCl4 stimulation, thereby promoting hepatic recruitment neutrophils subsequent damage. Furthermore, MBL-mediated protection CCl4-induced validated administration an MBL-expressing liver-specific adeno-associated virus, effectively ameliorated CCl4-treated MBL–/– mice. propose may be exploited new therapeutic approach treatment chemical-induced patients deficiency. chemically-induced