Effect Of ADMA On Maturation And Function Of Dendritic Cells Drived From Monocyte

ObjectiveAsymmetrical dimethylarginine(ADMA) is an inhibitor of nitric oxide synthesis(NOS) in vivo.Elevated plasma asymmetrical dimethylarginine(ADMA) is an independent risk factor for atherosclerosis(AS),which is recognized as inflammation and immune reactions.The purpose of this study is to approach the mechanism of the generation and progress of AS by investigating the effect of ADMA on the expression of DCs and the interaction between DCs and T lymphocytes.MethodsImmunophenotype,such as HLA-DR,CDla,CD86 and CD83,of ADMA-treated DCs was monitored by flow cytometry.The endocytic activity of ADMA-treated DCs was measured by flow cytometry using a FITC-dextran uptake assay.Allogeneic T cell activation by ADMA,treated DCs was tested by mixed lymphocyte reaction(MLR). The apoptosis activity of ADMA-treated DCs was measured by flow cytometry using a Annexin V-FITC.The expression of IL-10,IL-12 and TNF-αon ADMA-treated DCs was detected by immunofluorescence stain.Results The majority of immature DCs generated in control cultures with GM-CSF and IL-4 expressed high level of HLA-DR,moderate levels of CD1a and CD86,and low level of CD83,while the mature DCs exposed to LPS expressed high levels of HLA-DR, CD86 and CD83,moderate level of CD1a.The presence of ADMA did not change the phenotype of immature and high concentration ADMA inhibit the maturation of DCs. High concentration ADMA inhibit the endocytic activity of DC.Immature DCs in the presence of ADMA with high concentration were of less effective than control in stimulating T-cell proliferation.And immature DCs in the presence of ADMA with high concentration were of more effective than control in apoptosis.The expression of IL-10,IL-12 and TNF-αon DCs was significantly reduced by ADMA in a concentration-dependent manner as assessed by immunofluorescence stain.Conclusions High concentration ADMA is able to inhibit the maturatiom of DCs and inhibit the endocytic activity of DCs,and promote the apoptosis of DCs.ADMA can reduce the expression of IL-10,IL-12 and TNF-αon DCs.These indicate a novel pathophysiological mechanism for ADMA to promote atherogenesis.