White pulp compartments in the spleen of the turtle Mauremys caspica

Summary The aim of the present study was to analyze the nature of lymphoid and non-lymphoid cellular components occurring in distinct histological compartments of the splenic white pulp of the turtle, Mauremys caspica, in order to define their possible correlations with those of the spleen of higher vertebrates, principally mammals. The white pulp of M.caspica consisted of 3 clearly distinguishable regions: (1) the periateriolar lymphoid sheath, and (2) the inner and (3) the outer zones of the periellipsoidal lymphoid sheath. Reticular cells intimately associated with reticular fibres constituted an extensive meshwork in the periarteriolar lymphoid sheath which housed principally Ig-negative lyphoid cells, mature and immature plasma cells, and interdigitating cells. A few Ig-positive cells were also present in the peripheral region of the periarteriolar lymphoid sheath. The inner and outer zones of the periellipsoidal lymphoid sheath were separated by a discontinuous layer of reticular cell processes. In the inner zone, surface Ig-positive lymphoid cells predominated as well as dendritic cells, resembling ultrastructurally the mammalian follicular dendritic cells, although no germinal centres were found in the turtle spleen. Macrophages, some cytoplasmic Ig-positive cells, and Ig-negative lymphoid cells appeared in the outer zone of the periellipsoidal lymphoid sheath. These results allow us to speculate on a phylogenetic relationship between the periarteriolar lymphoid sheath and the inner and the outer zones of the periellipsoidal lymphoid sheath of the spleen of M. caspica and the periarteriolar lymphoid tissue, the lymphoid follicles and the marginal zone, respectively, of the mammalian splenic white pulp.     

大鼠中枢神经系统衰老的形态学研究Ⅳ.大脑皮质锥体细胞树突棘的数量变化

用6、12与31个月的雄性Wistar大鼠的大脑Krieg 2、3区皮质,对其V层大锥体细胞的五段50μm长度内的树突棘做形态学定量研究。在Golgi法的切片中共计数了三个年龄组的151个细胞的725段树突的棘密度。结果表明,老年大鼠比成年和青年大鼠的棘密度普遍下降。其中以基树突与侧树突棘度下降最显著(减少24％左右),顶树突只中段有明显减少。老年大鼠锥体细胞还常出现胞体、树突及其分支的明显形态改变。     

Growth of Ectopic Dendrites on Cortical Pyramidal Neurons in Neuronal Storage Diseases Correlates with Abnormal Accumulation of GM2 Ganglioside

Abstract: Ganglioside analysis and quantitative Golgi studies of the cerebral cortex of cats with ganglioside and nonganglioside lysosomal storage diseases reveal a correlation between the amount of accumulated GM2 ganglioside and the extent of ectopic dendrite growth on cortical pyramidal neurons. This correlation was not observed with any of the other gangliosides assayed for, including GM1 ganglioside. These results suggest a specific role for GM2 ganglioside in the initiation of ectopic neurites on pyramidal cells in vivo and are consistent with the developing hypothesis that different gangliosides have specific roles in different cell types dependent upon the receptor or other effector molecules with which they may interact.     

Engineering of zinc finger and MHC motifs to locked-in tertiary folds

The assembly of helical and -sheet peptide blocks containing reactive chain ends results inhighly branched chain architectures (locked-in folds) mimicking native tertiary structures.This molecular kit strategy allows to bypass the protein folding problem in protein de novodesign and gives access to protein mimetics of high thermodynamic stability. The validity ofthis concept is exemplified for the design and synthesis of locked-in folds mimicking the zincfinger and MHC folding motifs.     

Microtubules,dendritic spines and spine apparatuses

Summary Using techniques for enhanced microtubular preservation, including albumin pretreatment (Gray, 1975), occipital cortex of rats was studied electron microscopically at various ages of development. A close structural relationship was seen between microtubules, sacs of SER and the postsynaptic thickening in primordial spines and with the dense plate material of spine apparatuses. Stereoscopic preparations in addition show a more complicated substructure than previously described for the plate. Microtubules may contribute to the formation of the plate of the spine apparatus which in turn is associated with the postsynaptic thickening of the mature spine. Possible functional correlates are discussed.Dr. L.E. Westrum is an affiliate of the CDMRC at the University of Washington and a recipient of a Burroughs-Wellcome (USA) — Wellcome Trust (U.K.) Research Travel Grant. The research was also supported in part by NIH Grants NS 09678, NS 04053 (NINCDS) and DE 04942 (NIDR), DHHS     

Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C⁺MHCII^high DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.     

黑松三种菌根苗根系构型差异及其与生长的关系

为探讨林木不同菌根根系亚宏观结构对植物生长的影响,将黑松(Pinus thunbergii)分别接种黄色须腹菌(Rhizopogen luteous,简称Rl)、彩色豆马勃(Pisolithus tinctorius,简称 Pt2)和美味牛肝菌(Boletus edulis,简称Be)3种外生菌根菌,研究了不同菌根苗根系构型的差异及其与黑松生长的关系.结果表明,黑松3种菌根苗的根系参数(主根长、侧根总级数、一级侧根数量及直径、吸收根分布的范围、吸收根的数量及比表面积等)均比对照有不同程度的增加,且与黑松生长呈一定的正相关性;黑松不同处理菌根苗的根系整体构型差异显著:在生长最好的Rl菌根苗根系中,主根与侧根间具不同夹角的一级侧根分布均衡,且横向生长(80～90°)的侧根较多,其它角度(60～80°和<60°)的一级侧根依次递减,使整个根系呈""型,有效扩大了根系吸收的空间范围;生长相对较差的Be菌根苗其根系不同角度的一级侧根分布不均或80～90°的侧根较少;Pt2菌根苗生长较好,其根系构型界于前二者之间;而生长差的对照苗根最少,几乎没有80～90°的一级侧根.由此可见,不同菌根菌可通过影响根系的结构发育而影响黑松苗木的生长.     

抑制T细胞增殖的抗CD45单克隆抗体的建立

目的寻找能调节T细胞功能的相关分子,进行与T细胞介导的自身免疫性疾病相关的研究。方法从BALB/c小鼠骨髓中收集树突状细胞,免疫Wistar大鼠,进行细胞融合,建立杂交瘤细胞系。筛选得到很多株能调节T细胞功能的杂交瘤细胞系,对其中一株最能抑制T细胞增殖的杂交瘤细胞系进行了进一步的深入研究。结果显示其目标分子是CD45,同时增殖实验结果显示该抗体能显著抑制T细胞增殖反应。结论抗CD45单克隆抗体能有效抑制T细胞增殖,有望将本抗体用于T细胞介导的自身免疫性疾病的相关预防及治疗中。     

Emerging roles for retinoids in regeneration and differentiation in normal and disease states

The vitamin A (retinol) metabolite, all-trans retinoic acid (RA), is a signaling molecule that plays key roles in the development of the body plan and induces the differentiation of many types of cells. In this review the physiological and pathophysiological roles of retinoids (retinol and related metabolites) in mature animals are discussed. Both in the developing embryo and in the adult, RA signaling via combinatorial Hox gene expression is important for cell positional memory. The genes that require RA for the maturation/differentiation of T cells are only beginning to be cataloged, but it is clear that retinoids play a major role in expression of key genes in the immune system. An exciting, recent publication in regeneration research shows that ALDH1a2 (RALDH2), which is the rate-limiting enzyme in the production of RA from retinaldehyde, is highly induced shortly after amputation in the regenerating heart, adult fin, and larval fin in zebrafish. Thus, local generation of RA presumably plays a key role in fin formation during both embryogenesis and in fin regeneration. HIV transgenic mice and human patients with HIV-associated kidney disease exhibit a profound reduction in the level of RARβ protein in the glomeruli, and HIV transgenic mice show reduced retinol dehydrogenase levels, concomitant with a greater than 3-fold reduction in endogenous RA levels in the glomeruli. Levels of endogenous retinoids (those synthesized from retinol within cells) are altered in many different diseases in the lung, kidney, and central nervous system, contributing to pathophysiology. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.     

Prostaglandin E2 inhibits TNF production in murine bone marrow-derived dendritic cells

Exposure to pathogens induces dendritic cells to release inflammatory cytokines and chemokines. The inflammatory response is controlled by endogenous agents such as anti-inflammatory cytokines, glucocorticoids, anti-inflammatory neuropeptides, and lipid mediators. This study is the first report on the inhibition by prostaglandin E2 (PGE2) of TNF release from bone marrow-derived dendritic cells stimulated with lipopolysaccharide (LPS), a TLR4 ligand, or peptidoglycan, a TLR2 ligand. The inhibition of TNF occurs at both mRNA and protein level. The inhibitory effect of PGE2 is mediated by the EP2 and EP4 receptors, and involves both PKA signaling and mediation by DC-derived IL-10. Intraperitoneal administration of PGE2 together with LPS results in a reduction in serum TNF and intracellular TNF in peritoneal exudate cells, compared to LPS alone. In addition, administration of PGE2 in vivo reduces the numbers of CD11c+ DCc that accumulate in the peritoneal cavity in response to LPS. The various implications of the PGE2-induced reduction in TNF are discussed.