Induction of dendritic cell-mediated T-cell activation by modified but not native low-density lipoprotein in humans and inhibition by annexin a5: involvement of heat shock proteins.

OBJECTIVE: Atherosclerosis is an inflammatory disease, where activated immunocompetent cells, including dendritic cells (DCs) and T cells are abundant in plaques. Low-density lipoprotein modified either by oxidation (oxLDL) or by human group X-secreted phospholipase A2 (LDLx) and heat shock proteins (HSP), especially HSP60 and 90, have been implicated in atherosclerosis. We previously reported that Annexin A5 inhibits inflammatory effects of phospholipids, decreases vascular inflammation and improves vascular function in apolipoprotein E(-/-) mice. Here, we focus on the LDLx effects on human DCs and T cells. APPROACH AND RESULTS: Human DCs were differentiated from peripheral blood monocytes, stimulated by oxLDL or LDLx. Naive autologous T cells were cocultured with pretreated DCs. oxLDL and LDLx, in contrast to LDL, induced DC-activation and T-cell proliferation. T cells exposed to LDLx-treated DCs produced interferon-γ, interleukin (IL)-17 but not IL-4 and IL-10. Annexin A5 abrogated LDLx effects on DCs and T cells and increased production of transforming growth factor-ß and IL-10. Furthermore, IL-10 producing T cells suppressed primary T-cell activation via soluble IL-10, transforming growth factor-ß, and cell-cell contact. Lentiviral-mediated shRNA knock-down HSP60 and 90 in DCs attenuated the effect of LDLx on DCs and subsequent T-cell proliferation. Experiments on DC and T cells derived from carotid atherosclerotic plaques gave similar results. CONCLUSIONS: Our data show that modified forms of LDL such as LDLx but not native LDL activate human T cells through DCs. HSP60 and 90 contribute to such T-cell activation. Annexin A5 promotes induction of regulatory T cells and is potentially interesting as a therapeutic agent.

Crystal structure of bis-{2-[bis-(2-hy-droxy-eth-yl)amino]-ethanol-κ(3) O,N,O'}zinc terephthalate.

In the title salt, [Zn(C6H15NO3)2](C8H4O4), the Zn(II) cation, located on a centre of inversion, is coordinated by four O atoms and two N atoms from two tridentate 2-[bis-(2-hy-droxy-eth-yl)amino]-ethanol (BHEA) ligands, giving rise to a slightly distorted octa-hedral geometry. The terephthalate dianion, located about a centre of inversion, is not coordinated to Zn(II) but is connected through O-H⋯O contacts with [Zn(BHEA)2](2+) cations, leading to a three-dimensional crystal structure.

Crystal structure of bis-{2-[bis-(2-hy-droxy-eth-yl)amino]-ethanol-κ(4) O,N,O',O''}cadmium terephthalate.

In the title salt, [Cd(C6H15NO3)2](C8H4O4), the Cd(2+) cation is coordinated by six O atoms and two N atoms from two tetra-dentate 2-[bis-(2-hy-droxy-eth-yl)amino]-ethanol ligands, displaying a distorted square-anti-prismatic coordination. The terephthalate dianion does not coordinate to the cation but is connected through O⋯H-O hydrogen bonds of medium strength to the complex cations, leading to a layered structure extending parallel to (100).

Crystal structure of bis-{2-[(2-hy-droxy-eth-yl)amino]-ethanol-κ(3) O,N,O'}copper(II) terephthalate.

The mol-ecular components of the title salt, [Cu(C4H11NO2)2](C8H4O4), are one Cu(II) cation O,N,O'-chelated by two tridentate 2-[(2-hy-droxy-eth-yl)amino]-ethanol ligands, and a terephthalate counter-dianion, located about a centre of inversion. The complex Cu(II) cation is located about a centre of inversion and shows typical Jahn-Teller distortion, with two short Cu-O and two short Cu-N bonds in the equatorial plane and two long Cu-O bonds to the axial atoms. The cations are arranged in sheets parallel to (100), with the centrosymmetric terephthalate anions located between the sheets. Each anion is the acceptor of four O-H⋯O and two N-H⋯O hydrogen bonds, forming a three-dimensional network structure.

Crystal structure of poly[[µ3-4,4'-(4,4'-bipyridine-2,6-diyl)dibenzoato]{µ2-4-[6-(4-carboxyphenyl)-4,4'-bipyridin-4'-ium-2-yl]benzoato}manganese(II)] hemi-hydrate].

The title compound, {[Mn(C24H14N2O4)(C24H16N2O4)]·0.5H2O} n , was obtained by the reaction of manganese nitrate with the ligand 4,4'-(4,4'-bi-pyridine-2,6-di-yl) di-benzoic acid under hydro-thermal conditions. The water O atom is located on a twofold rotation axis. The Mn(2+) ion is hepta-coordinated by six O atoms and one N atom from the ligands. In this structure, the ligands adopts two different forms, one completely deprotonated and one with a protonated N atom (pyridinium) and a carboxylic acid function. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds consolidate the packing, forming a three-dimensional framework.

Crystal structure of poly[[{µ2-1,4-bis[(1H-imid-azol-1-yl)methyl]benzene}[µ6-5-(4-carboxylatophenoxy)isophthalato]-µ3-hydroxido-dicobalt(II)] 0.25-hydrate].

The title coordination polymer, {[Co2(C15H7O7)(OH)(C14H14N4)]·0.25H2O} n , was synthesized under hydro-thermal conditions. The asymmetric unit contains two Co(2+) ions, one L (3-) anion originating from 5-(4-carb-oxy-phen-oxy)isophthalic acid (H3 L), one OH(-) ligand, one 1,4-bis-[(1H-imidazol-l-yl)meth-yl]benzene (bix) ligand and one disordered lattice water mol-ecule (occupancy 0.25). The two Co(2+) ions have different environments. One has an octa-hedral O4N2 coordin-ation sphere, defined by four O atoms from three carboxyl-ate groups and one OH(-) ligand, and two N atoms from two symmetry-related bix ligands. The other has a trigonal-bipyramidal O5 coordination sphere resulting from three carboxyl-ate groups and two OH(-) ligands. The dihedral angles between the two benzene rings in the L (3-) ligand and between the benzene ring and the two imidazole rings in the bix ligand are 67.05 (15), 75.27 (17) and 82.05 (17)°, respectively. Four neighbouring Co(2+) ions are linked by six carboxyl-ate groups and two µ 3-OH ligands, forming a butterfly-shaped secondary building unit (SBU). These SBUs are connected by L (3-) anions into layers parallel to (1-10). Adjacent layers are cross-linked by the bix ligands, forming a three-dimensional framework that has a bimodal (3,8)-connected tfz-d topology. The disordered lattice water mol-ecule is located in the voids of the framework and has O⋯O and O⋯N contacts of 2.81 (2) and 2.95 (2) Å, suggesting medium-strength hydrogen bonds. The title compound may be a good candidate for artificial eye lenses.

Crystal structure of bis-{µ-4,4'-[1,3-phenyl-enebis(-oxy)]dibenzoato-κ(4) O,O':O'',O'''}bis[(1,10-phenanthroline-κ(2) N,N')zinc(II)] dihydrate.

Two 4,4'-[1,3-phenyl-enebis(-oxy)]dibenzoate anions bridge two 1,10-phenanthroline-chelated Zn(II) cations about a center of inversion to generate the dinuclear title compound, [Zn2(C20H12O6)2(C12H8N2)2]·2H2O. The geometry about the Zn(II) atom is a distorted octa-hedron. In the crystal, the mol-ecules are connected by classical O-H⋯O hydrogen bonds, weak C-H⋯O hydrogen bonds and C-H⋯π inter-actions, forming a three dimensional network. π-π stacking is also observed between aromatic rings of adjacent mol-ecules, centroid-centroid distances are 3.753 (2), 3.5429 (16) and 3.5695 (17) Å.