Bcl6, a sequence-specific transcriptional repressor, is important for generation and maintenance of memory CD8 + T cells. Although memory CD8 + T cells are generated from effector CD8 + T cells, a role for Bcl6 in effector CD8 + T cells is largely unknown. We show here that Bcl6 expression was transiently induced in activated CD8 + T cells and continuously up-regulated in effector CD8 + T cells. The amount of granzyme B mRNA among effector molecules produced by effector CD8 + T cells inversely correlated with the amount of Bcl6 mRNA in CD8 + T cells. Overexpression of Bcl6 in CD8 + T cells resulted in lower killing activity at their effector phase, supporting the reduction of granzyme B expression in effector CD8 + T cells by Bcl6. We identified a putative Bcl6-binding DNA sequence in the promoter region of the granzyme B gene. Binding of Bcl6 to the Bcl6-binding sequence was detected in naive CD8 + T cells but not in activated CD8 + T cells by chromatin immunoprecipitation assay. Furthermore, the Bcl6-binding sequence was required for Bcl6 to repress the luciferase reporter gene expression controlled by the granzyme B promoter. Thus, the granzyme B gene is a molecular target of Bcl6 in effector CD8 + T cells.
Sphingosylphosphorylcholine (SPC) increased intracellular Ca 2+ concentration ([Ca 2+ ]i) and nitric oxide (NO) production in endothelial cells in situ on bovine aortic valves, and induced endothelium-dependent relaxation of bovine coronary arteries precontracted with U-46619. The SPC-induced vasorelaxation was inhibited by N g -monomethyl-L-arginine, an inhibitor of both constitutive and inducible NO synthase (NOS), but not by 1-(2-trifluoromethylphenyl) imidazole, an inhibitor of inducible NOS (iNOS). Immunoblotting revealed that endothelial constitutive NOS, but not iNOS, was present in endothelial cells in situ on the bovine aortic valves. We propose that SPC activates [Ca 2+ ]i levels and NO production of endothelial cells in situ, thereby causing an endotheliumdependent vasorelaxation.z 1999 Federation of European Biochemical Societies.
The mechanisms of fluid penetration through the gabbroic lower crust are important for the hydration of oceanic lithosphere. In the Oman ophiolite, which preserves an entire sequence of oceanic lithosphere formed at a fast-spreading ridge, the layered gabbros and dunites are extensively serpentinized. In this paper, we describe the characteristic textures of serpentinized troctolite and olivine gabbros recovered from the CM1A site of the Oman Drilling Project. In the troctolite, an olivine mesh texture is pervasively developed and is characterized by two types of veins: early lizardite + brucite + magnetite and late Al-rich lizardite + magnetite. These veins suggest the initiation of serpentinization at <350°C and a supply of Si and Al from plagioclase during the later stages of serpentinization. Plagioclase surrounding serpentinized olivine grains commonly shows radial fracturing. Numerical simulations using the discrete element method applied to coupled fluid flow, reaction, and fracturing reveal that volume expansion of olivine grains during serpentinization results in the simultaneous fracturing of olivine and surrounding plagioclase, and that the thermal stress during cooling of oceanic lithosphere might also cause preferential olivine fracturing prior to serpentinization. The simulations also predict a self-organizing fracture network that connects the olivine grains and passes through both olivine-rich and olivine-poor layers, resulting in permeability enhancement during serpentinization. Our results suggest that reaction-induced fracturing plays an essential role in the infiltration of seawater through the lower crust and into the mantle within oceanic lithosphere. Plain Language Summary The Oman ophiolite preserves evidence of pervasive serpentinization of the lower crust, Moho transition zone, and uppermost mantle. In this study, we investigated a troctolite and olivine gabbros from the CM1A site of the Oman Drilling Project, and compared fracture patterns in these rocks with those predicted by discrete element method (DEM) numerical simulations. In the troctolite, olivine grains are serpentinized to form a mesh texture, and radial fractures are developed in plagioclase and clinopyroxene adjacent to olivine. The olivine mesh texture consists of two types of veins: early serpentine + brucite + magnetite and late Al-rich serpentine + magnetite. Numerical simulations of coupled fracturing, reaction, and fluid flow reproduced the observed fracture patterns and indicate that reaction-induced fracturing plays a key role in permeability enhancement within the lower oceanic crust during low-temperature alteration.
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