Effect of inosine monophosphate dehydrogenase inhibitor on chemotaxis, migration and endocytosis of human peripheral myeloid dendritic cells / 中华肝胆外科杂志

ABSTRACT

Objective To study the effect of inosine monophosphate dehydrogenase inhibitor (IMPDHI) on chemotaxis, migration and endocytosis of human peripheral myeloid dendritic cells (MDCs). Methods Freshly isolated peripheral blood mononuclear cells(PBMC)collected from healthy volunteers (N=15) and the study group were treated with IMPDHI. CC chemokine receptors on MDCs were analyzed by flow cytometry. The study group, control group and different chemokines were added via trans-well approach for different chemokines, stained by Lin-1/CD11c/HLA-DR and counted by flow cytometry. The migration index was calculated as a percentage of MDC migrated in response to the tested chemokine. After isolation of blood dendritic cell antigen-1+ (BDCA-1+ ), mannose receptor-mediated endocytosis was measured as the cellular uptake of FITC-dextran by the flow cytometry. Results (1) Compared to the control group, the expression of CCR1 in the study group was up-regulated significantly(17.02±3.23～30.63±9.13, P＜0.05) and the expressions of CCR3(10.26±2.25～5.81±0.97 P＜0.05) and CCR7 (9.56± 1.84～5.18±0.60 P＜0.05)were downregulated significantly. MDCs in the study group showed enhanced migratory response to inflammatory chemokine CCL2, CCL3, CCL4, CCL7 and CXCL12 (P＜0.05). (2)The endocytosis capacity in the study group was significantly higher than that in control group (P ＜0.05). Conclusion IMPDHI enhances the endocytotic capacity of MDCs and impairs the migratory response of peripheral MDCs to lymphocytic tissue by up-regulating the expression of chemokine receptor in MDCs and enhancing migratory response to inflammatory chemokines.