[The activation of CD11b by leukadherin-1 alleviates endotoxic shock through promoting the aggregation and activation of myeloid-derived suppressor cells].

Objective To study the effect of CD11b agonist leukadherin-1 (LA1) on the aggregation and immunosuppressive function of myeloid-derived suppressor cells (MDSCs) and its therapeutic effect on the condition of endotoxic shock mice. Methods The percentages of MDSCs , granulocytic myeloid-derived suppressor cells(G-MDSCs)and monocytic myeloid-derived suppressor cells(M-MDSCs)in spleen were detected by flow cytometry, after C57BL/6 female mice were injected of LA1 to activate through abdominal cavity for 12 hours and 48 hours. MDSCs were induced from the femur and tibia of C57BL/6 female mice in vitro. The expression levels of immunosuppressive related factors, such as interleukin 10 (IL-10), NADPH oxidase 1 (NOX1) and inducible nitric oxide synthase (iNOS) , were detected by real time quantitative PCR. C57BL/6 female mice were randomly divided into PBS group, LA1 group, PBS combined LPS group and LA1 combined LPS group. Flow cytometry was utilized to detect the ratio changes of MDSCs, G-MDSCs and M-MDSCs as well as the expression of CD86 and CD40 in macrophage, hematoxylin-eosin staining of lung and liver was utilized to detect the pathological injury, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL)was used to detect the apoptosis of pneumonocyte and hepatocyte and mortality analysis was reflected the severity of the disease. Based on the above indicators, we analyzed the effects of LA1 on the aggregation of MDSCs and the condition of mice in endotoxic shock. Results The ratio of MDSCs was increased by LA1 treatment for 12 and 48 hours. Further analysis of the proportions of G-MDSCs showed that LA1 treatment for 12 hours increased the proportions of G-MDSCs compared with the control group. In vitro, mRNA levels of IL-10, NOX1 and iNOS were increased after LA1 treatment in MDSCs. In vivo experiments, compared with the PBS combined LPS group, the proportions of MDSCs and G-MDSCs in LA1 combined LPS group were increased, the injuries of liver and lung were alleviated, the mortalities were reduced, and the activations of macrophage were decreased. Conclusion The activation of CD11b by LA1 alleviates endotoxin shock by promoting the aggregation of MDSCs and the expression of immunosuppressive related factors.