The impact of inosine monophosphate dehydrogenase inhibitor on human peripheral myeloid dendritic cell
10.3760/cma.j.issn.0254-5101.2010.11.001
- VernacularTitle:次黄嘌呤单核苷酸脱氢酶抑制剂对人外周髓样树突状细胞功能影响的研究
- Author:
Jing HOU
;
Danian TANG
;
Yongguo LI
;
Xiuwen HE
;
Yuan XU
;
Junmin WEI
- Publication Type:Journal Article
- Keywords:
Inosine monophosphate dehydrogenase inhibitor;
Maturation;
Endocytotic capacity;
Migration;
Cell proliferation
- From:
Chinese Journal of Microbiology and Immunology
2010;30(11):977-981
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of inosine monophosphate dehydrogenase inhibitor (IMPDHI) on maturation, migration, endocytosis and allostimulatory properties of human peripheral myeloid dendritic cell (MDC). Methods PBMC from healthy donors were isolated. MDC were cocultured with PBMC and exposed to mycophenolic acid (MPA) for 48 h. The expression of co-stimulatory and adhesion molecules as well as chemokine receptors on MDC was analyzed by flow cytometry. In separate experiments,MDC were cultured with or without MPA, and their endocytosis function was estimated by means of FITC dextran uptake. MDC migration experiments were performed in Transwell chambers. Inflammatory chemo kines were added to the lower chambers and MDC numbers were analyzed by flow cytometry. MPA treated (48 h) BDCA-1 + DC served as stimulator cells in MLR. Allogenic healthy CD4 T responder cells were labeled with fluorescent dye CFSE and measured by flow cytometry. Results Maturation: compared to the control group, the expression of CD40, CD62L, HLA-DR, CD54, CD80, CD83 and CD86 on MDC in study group were significantly down-regulated ( P ＜ 0.05 ). Chemokine receptor and migration: compared to control group, the expression of CCR1 on MDC in study group was up-regulated significantly (17.02 ±3.23 vs 30.63 ± 9.13, P ＜ 0.05 ), the expression of CCR3 ( 10.26 ± 2.25 vs 5.81 ± 0.97, P ＜ 0.05 ) and CCR7(9.56 ± 1.84 vs 5.18 ±0.60, P ＜0. 05) on MDC were down-regulated significantly in the study group.MDC in study group showed enchanced migratory response to inflammatory chemokine CCL2, CCL3, CCL4,CCL7, CXCL12 (P＜0.05). Endocytotic capacity: the capacity of endocytosis in study group was signifi cantly higher than that in control group( P ＜ 0.05 ). Llostimulatory capacity: MPA-treated MDC exhibited a markedly reduced ability to stimulate allogenic CD4+ T cell proliferation. Conclusion Treatment of MDC with MPA exhibited an immature phenotype, a propensity to migrate in response to inflammatory chemokines, increased endocytotic capacity and impaired allogenic ability of MDC.
