B cell-activating factor of the tumor necrosis factor (TNF) family, or BAFF, is mainly produced in monocytes and dendritic cells, and indispensable for proliferation, differentiation and survival of B cells. BAFF is a type II membrane-bound protein and the extracellular C-terminal fragment is released from the cells as soluble BAFF (sBAFF), which binds to specific receptors on B cells. Accumulating evidence suggests that BAFF plays an important role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE). In this study, we developed a sensitive sandwich ELISA system to quantify the amount of sBAFF using our own mAb. Treatment of peripheral T cells of SLE patients with an anti-CD3 antibody triggered robust expression of BAFF and subsequent release of sBAFF from the cells. On the other hand, the stimulus induced only marginal elevation of sBAFF from normal T cells.

Aim: A sedentary lifestyle with insufficient exercise is associated with cardiovascular disease. Previous studies have demonstrated that endurance exercise benefits atherosclerosis and cardiovascular disorders; however, the mechanisms by which physical activity, such as voluntary exercise (Ex), produces these effects are not fully understood. Methods and Results: Eight-week-old male apolipoprotein (ApoE)-deficient mice were fed a standard diet (STD) or high fat diet (HFD) for 10 weeks. The HFD Ex group mice performed Ex on a running wheel for 10 weeks. No significant differences in lipid profiles were observed between the HFD and HFD Ex groups. Although changes in body and brown adipose tissue weights were comparable between the HFD and HFD Ex groups, white adipose tissue weight was significantly lower in the HFD Ex group than in the HFD group. The areas of atherosclerotic lesions in the aortic sinus and thoracoabdominal aorta were significantly reduced in the HFD Ex group than in the HFD group (p 0.001). There was a strong negative correlation between atherosclerotic areas and the mean running distance per day in the HFD Ex group (r 0.90, p 0.01). Endothelial function was significantly preserved in the HFD Ex group (p 0.05). Serum interleukin-6 and macrophage chemoattractant protein-1 levels were significantly lower and those of adiponectin were significantly higher in the HFD Ex group than in the HFD group (p 0.05). Conclusions: These results suggest that Ex ameliorates the progression of endothelial dysfunction and atherosclerotic lesion formation through anti-inflammatory effects, despite continued consumption of HFD.

A new type of glycolipid, phosphatidylglucoside (PtdGlc), was identified as a component of raft-like membrane domains of the human leukemia cell line HL-60. In this study, we show that PtdGlc forms functional domains that are different from those produced by lactosylceramide (LacCer)-enriched lipid rafts. These rafts initiate neutrophil apoptosis. Neutrophils are the only type of human peripheral blood leukocyte or monocyte-derived dendritic cell to express large amounts of PtdGlc on their cell surfaces. PtdGlc was not colocalized with LacCer. Anti-PtdGlc IgM DIM21 did not induce neutrophil chemotaxis or superoxide generation, whereas anti-LacCer IgM T5A7 induced these activities. DIM21, but not T5A7, significantly induced neutrophil apoptosis. DIM21-induced apoptosis was inhibited by specific inhibitors of cysteine-containing aspartate-specific proteases (caspases)-8, -9, and -3 but not by the Src family kinase inhibitor PP1, PIP3 kinase inhibitor LY294002, NADPH oxidase inhibitor diphenyleneiodonium, superoxide dismutase, or catalase. PtdGlc was colocalized with Fas on the neutrophil plasma membrane. DIM21 and the agonist anti-Fas Ab DX2 induced the formation of large Fas-colocalized clusters of PtdGlc on the plasma membrane. Furthermore, the antagonistic anti-Fas Ab ZB4 significantly inhibited DIM21-induced neutrophil apoptosis. These results suggest that PtdGlc is specifically expressed on neutrophils and mediates apoptosis of these cells, and that the Fas-associated death signal may be involved in PtdGlc-mediated apoptosis.

B cell activating factor of the TNF family, or BAFF, is a type II membrane-bound protein and the extracellular C-terminal fragment is released from the cells as soluble BAFF (sBAFF). BAFF is mainly produced in monocytes and dendritic cells, and regulates proliferation, differentiation, and survival of B cells. Our recent study has revealed that the expression of BAFF is abnormally elevated in peripheral T cells of SLE patients, suggesting that BAFF plays an important role in the pathogenesis of autoimmune diseases. In the present study, we investigated the expression of BAFF in T cells of Sjögren’s syndrome (SS), and found that the expression of BAFF was enhanced in peripheral T cells of SS patients upon stimulation. We further analyzed the mechanism of release of sBAFF from T cells, since this step may provide a therapeutic possibility to treat the diseases. Particularly, we focused on furin and matrix metalloproteinases, which are membrane bound proteases and responsible for shedding of several proteins. Investigation with specific inhibitors against these proteases revealed that at least furin and MMP9 was involved in the release of sBAFF.

Background: Acute coronary syndrome (ACS) is an amplified state of inflammation and immune reaction. Dendritic cells (DCs) expressing various Toll-like receptors (TLRs) have been observed in atherosclerotic lesions, however, the clinical significance of DCs in pathogenesis of ACS has not been completely investigated. Methods: Ten patients with ACS and 10 patients with stable angina pectoris (SAP) were enrolled in this study. Monocyte-derived DCs were generated from CD14 + cells by culturing with granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 for 6 days. Expression of cell surface CD86 and CD83 were measured by flowcytometry. Expression of genes, including CD86, CD83, CCL19, CCR7, TLR2, TLR4, TLR5, TLR8, and TLR9, were measured by real-time PCR. Plasma IL-6 and tumor necrosis factor (TNF)- levels were also measured. Results: The number of CD86 + CD83 + DCs in the ACS group was significantly higher than that in the SAP group (P < 0.05). Expression levels of CD86, CD83, CCL19, CCR7, TLR2, TLR4, and TLR9 in the ACS group were significantly higher than those in the SAP group (all, P < 0.05). Plasma IL-6 and TNF- levels in the ACS group were significantly higher than those in the SAP group (all, P < 0.05). In addition, a positive correlation was observed between the number of CD86 + CD83 + cells and plasma levels of IL-6 (r = 0.88, P < 0.0001) as well as between the number of CD86 + CD83 + cells TNF- levels (r = 0.78, P < 0.0001). Conclusions: These results demonstrated that monocyte-derived DCs are activated in patients with ACS, suggesting that activated DCs may play an important role in the pathogenesis of ACS.