Tonic B cell activation by Radioprotective105/MD-1 promotes disease progression in MRL/lpr mice

Toll-like receptors (TLRs) have a crucial role in sensing microbial products and triggering immune responses. Recent reports have indicated that TLR7 and TLR9 have an important role in activating autoreactive B cells. In addition to TLR7 and TLR9, mouse B cells express TLR2, TLR4 and structurally related Radioprotective105 (RP105). We have previously shown that RP105 works in concert with TLR2/4 in antibody response to TLR2/4 ligands. We here report that B cells are constitutively activated by TLR2/4 and RP105. Such B cell activation was revealed by the γ3 germ line transcript and serum IgG3 production, both of which were impaired by the lack of RP105 or TLR2/4. Serum IgG3 was not altered in germ-free or antibiotics-treated mice, suggesting that the microbial flora hardly contributes to the continuous activation of B cells. The lack of RP105-dependent B cell activation ameliorated disease progression in lupus-prone MRL/lpr mice. RP105−/− MRL/lpr mice showed less lymphoadenopathy/splenomegaly and longer survival than MRL/lpr mice. Whereas glomerulonephritis and auto-antibody production were not altered, improvement in blood urea nitrogen and lower incidence of renal arteritis indicated that renal function was ameliorated in the absence of RP105. Our results suggest that RP105-dependent tonic B cell activation has a pathogenic role in MRL/lpr mic

The Intensity of Satellite Reflections in Electron Diffraction Patterns from Evaporated Alloy Films with CuAu II Type Superstructure

In order to elucidate the origin of satellite reflections flanking the direct spot in the electron diffraction pattern of a single crystal evaporated film with CuAu II type superlattice, the peak as well as integrated intensities have been measured as functions of the wavelength of electrons corresponding to the accelerating voltage from 75 to 280KV. It has been revealed that the intensity of the satellite in question relative to a fundamental reflection consists of two parts, a major part which depends on the wavelength in such a way as predicted by the theory of multiple reflection, and the other minor part which is independent of the wavelength. The existence of the latter part shows that the reflection is not a forbidden one and, therefore, a lattice modulation accompanies the regular anti-phase structure. Fourier potential due to this lattice modulation, V_s, is estimated to be in the order of one tenth the magnitude of V_ Some consideration concerning the nature of the modulation is given by comparing the results of electron and X-ray diffraction studies

Protective effect of FK506 and Thromboxane synthase inhibitor on ischemia-reperfusion injury in non-heart-beating donor in rat orthotopic liver transplantation

The study investigated the possibility of pharmacologically modulating hepatic allograft function from non-heart-beating donors (NHBDs)using male Lewisrats. The donors were divided into 4 groups :Group 1 in which the vehicle was administered, Group 2 in which FK506 (tacrolimus a powerful immunosuppressive agent)was administered,Group3 in which OKY046 (a specific thromboxane synthetase inhibitor) was administered and Group 4 in which FK506 and OKY046 were administered. The recipients received orthotopic liver transplantation. The survival rates differed significantly between the recipients that had received liver transplantation from Groups1 and 4. The serum liver enzyme and inflammatory cytokine concentrations of the recipients which had received liver transplantation from Groups 2, 3 and 4 were significantly lower than those of the recipients that had received liver transplantation from Group1. Although there was no significant difference, all parameters were better in the recipients that had received transplantation from Group 4 than those that had received transplantation from Groups 2 and 3. The action mechanisms of FK506 and OKY046 are completely different. Therefore, concomitant use of FK506 and OKY046 might have additive effects on liver transplantation from NHBDs. In conclusion, we demonstrated that pretreatment of NHBDs using FK506 and OKY 046 ameliorated graft viability