Anti-CD24 antibody exacerbates the ConA-induced acute liver injury in mice

Abstract

Objective To investigate the effects of anti-CD24 antibody on concanavalin A (ConA)-induced acute liver injury in mice and to analyze the possible molecular mechanism. Methods A mouse model of acute liver injury was established by injecting wild-type (WT) mice with ConA alone (as control group) or in combination with (as experimental group) anti-CD24 antibody. Liver tissues were stained with hematoxylin and eosin (HE staining) for histological examination. Levels of alanine transaminase (ALT) in serum samples were measured. Flow cytometry analysis was performed to detect different macrophages subsets in mice liver tissues. Tumor necrosis factor-α (TNF-α) secreted by M1 macrophages was detected by intracellular cytokine staining and flow cytometry analysis. Results Hepatomegaly was observed in mice from the experimental group. Massive liver hemorrhage, spotty necrosis and inflammatory infiltration were observed in liver tissues of mice co-injected with ConA and anti-CD24 antibody. The levels of ALT in serum samples collected from the mice of the experimental group were higher than those of the control group (P<0.001). Results of the flow cytometry analysis showed that the percentages of M1 Kupffer cells (KC) increased significantly in mice from the experimental group (P<0.01), while no significant changes were observed in the percentages of M2 KC. Moreover, treating mice with anti-CD24 antibody significantly enhanced the secretion of TNF-α by KC as indicated by flow cytometry analysis (P<0.001). Conclusion This study suggests that anti-CD24 antibody could exacerbate the ConA-induced acute liver injury in mice, which might relate to the enhanced secretion of TNF-α by M1 KC. The underlying mechanisms are under investigation. Key words: CD24; Concanavalin A; Acute liver injury; Kupffer cell (KC); TNF-α