[Effects and mechanism of hyperglycemia on development and maturation and immune function of human monocyte derived dendritic cells].
OBJECTIVE
Dendritic cells play an important role in the pathogenesis of atherosclerosis. To explore the effects of hyperglycemia on the maturation and immune function of human monocyte derived dendritic cells (MDCs).


METHODS
Immature MDCs were cultured in RPMI1640 medium with either 5.5 mmol/L D-glucose (NG), 25 mmol/L D-glucose (HG) or 5.5 mmol/L D-glucose + 19.5 mmol/L mannitol (HM) in the absence or presence of 30 mmol/L N-acetylcysteine [NAC, a reactive oxygen species inhibitor (ROS)] for 48 hours. FACS was used to investigate the MDCs immunophenotypic expression. Immune function was evaluated by allogeneic mixed T lymphocyte reaction and measurement of cytokine levels from culture supernatants. Intracellular ROS production in MDCs was also measured by 2', 7'-dichlorodihydrofluorescein (DCF, 10 micromol/L) fluorescence using confocal laser-scanning microscopy techniques.


RESULTS
Compared with NG and HM treated MDCs, the expression of maturation markers such as CD1a, HLA-DR, CD83, CD86 were significantly upregulated, allogeneic T cells proliferation as well as the cytokines secretions (IL-2, IL-12, IL-10 and IFN-gamma) significantly increased in HG treated MDCs. Intracellular ROS production in MDCs was also significantly increased and all these stimulatory effects of HG could be partially attenuated by NAC.


CONCLUSIONS
High glucose promote the maturation of MDCs and augment their capacity to stimulate T-cell proliferation and cytokine secretions at least in part through enhancing intracellular ROS generation. These stimulating effects of high glucose on MDCs maturation may be one of the mechanisms of accelerated atherosclerosis found in patients with diabetes.
Yao
Kang
K
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Disease, Shanghai 200032, China.
Ge
Jun-bo
JB
Sun
Ai-jun
AJ
Hong
Xiao-wu
XW
Shi
Hong-yu
HY
Huang
Rong-chong
RC
Jia
Qing-zhe
QZ
Wang
Ke-qiang
KQ
Zhong
Cui-ping
CP
Cao
Xue-tao
XT
Zou
Yun-zeng
YZ
D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005947:Glucose / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D009000:Monocytes / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology
D003470:Culture Media; D016207:Cytokines; D017382:Reactive Oxygen Species; D005947:Glucose