Neuronal Regulation of Interleukin 6 Secretion in Murine Spleen: Adrenergic and Opioidergic Control

Abstract: The PNS was anticipated to be involved in the modulation of immune responses. To study aspects of this neuronal-immune communication, a recently developed tissue slice method was used to study the effects of adrenergic and opioidergic transmitters on interleukin 6 (IL-6) secretion in the spleen. The α₂-adrenergic agonist p -aminoclonidine (10⁻⁷ M ) inhibited IL-6 secretion (control vs. p -aminoclonidine, 100.0 ± 4.76 vs. 59.3 ± 6.6% of control values; p < 0.001). The α₁-adrenergic agonist methoxamine (10⁻⁸ M ) also inhibited IL-6 secretion (100.0 ± 4.8 vs. 71.5 ± 3.8%; p < 0.001). The endogenous opioids β-endorphin (10⁻¹⁰ M ), methionine-enkephalin (10⁻⁹ M ), and leucine-enkephalin (10⁻⁹ M ) inhibited IL-6 secretion as well ( p = 0.0051, p = 0.0337, and p = 0.0226, respectively). Electrical stimulation of spleen slices inhibited IL-6 secretion (100.0 ± 4.3 vs. 56.7 ± 4.6% of control values; p < 0.001). The involvement of α-adrenergic and opioidergic molecules in this electrically induced inhibition was shown by the use of antagonists. Electrical inhibition of IL-6 secretion was attenuated by phentolamine (10⁻⁷ M ; p = 0.0345), by naloxone (10⁻⁶ M ; p = 0.0046), by cyprodime (10⁻⁸ M ; p = 0.0014), and by the combination of cyprodime (10⁻⁷ M ) plus phentolamine (10⁻⁸ M ; p < 0.0001). We conclude from the complementary studies that the inhibition of IL-6 secretion induced by electrical pulses was mostly mediated by α-adrenergic and μ-opioidergic endogenous transmitters.     

Characterization of non-lymphoid cells in the white pulp of the mouse spleen: An in vivo and in vitro study

Summary Non-lymphoid cells (marginal metallophils, follicular immunecomplex-retaining cells, interdigitating cells), which are present in certain areas of the white pulp in the mouse spleen were characterized by means of (immuno)enzyme histochemical techniques, carbon uptake and experiments with lethal X-irradiation. Marginal metallophils are clearly present at the inner border of the marginal zone and show a very strong, E-600 sensitive, non-specific esterase (NSE) activity. Follicular immune-complex-retaining cells show a weak and diffuse NSE activity and no carbon uptake as shown by the combined application of an immunohistoperoxidase technique (for the demonstration of immune complexes), enzyme histochemistry (for NSE activity) and carbon uptake (for phagocytosis). Interdigitating cells show a distinct focus of NSE activity in the cytoplasm, weak carbon uptake and high radiation sensitivity. Demonstration of NSE activity is useful for the identification of the different non-lymphoid cells in the white pulp of the mouse spleen. It is suggested that the in vitro observed dendritic cells of Steinman and Cohn (1973) belong to the mononuclear phagocyte system, as transitional cells are encountered with cytological features of both dendritic cells and macrophages. These in vitro dendritic cells (or a portion of them) are probably similar to the interdigitating cells.Abbreviations HRP horseradish peroxidase - IDC interdigitating cells - PALS periarteriolar lymphocytic sheath - NSE non-specific esterase     

FGF-1改构体对小鼠脾细胞增殖与凋亡的影响

目的:主要探讨非促分裂改构人酸性成纤维细胞生长因子(MrhFGF-1)对balb／c小鼠脾细胞增殖和凋亡的影响。方法:采用3H-TdR掺入的方法检测MrhFGF-1同野生型hFGF-1相比对脾细胞增殖的影响,实验组分为(1)对照组;(2)FGF-1处理组;(3)ConA处理组;(4)FGF-1+ConA处理组。用流式细胞仪定量分析MrhFGF-1对脾细胞的凋亡保护作用,(1)对照组;(2)DEX处理组;(3)DEX+FGF-1(hFGF-1、rhFGF-1、MrhFGF-1)处理组。结果表明,利用DNA重组技术构建的一种非促分裂FGF-1突变体MrhFGF-1和野生型FGF-1相比,对脾细胞的促细胞增殖能力明显降低,但其对细胞凋亡保护作用的影响并无显著性变化,说明FGF-1的促细胞增殖能力和细胞凋亡保护信号通路并非由同一信号通路来实现的。     

Trypanosoma brucei brucei: A comparison of gene expression in the liver and spleen of infected mice utilizing cDNA microarray technology

Trypanosoma brucei brucei, the infectious agent of the disease known as Nagana, is a pathogenic trypanosome occurring in Africa, where it causes significant economic loss to domesticated livestock. Although many studies on the histopathology of organs of mice infected with T. b. brucei have been reported, little work has been done regarding gene expression in these organs in infected mice. In this paper, we describe the use of cDNA microarray to determine gene expression profiles in the liver and spleen of mice infected with T. b. brucei (STIB 920) at peak parasitaemia (12 days after infection). Our results showed that a total of 123 genes in the liver and 389 genes in the spleen were expressed differentially in T. b. brucei infected mice. In contrast, however, in an acute infection in mice caused by Trypanosoma brucei evansi, a species genetically related to T. b. brucei, 336 genes in the liver and 190 genes in the spleen were expressed, differentially, indicating that the liver of mice was more affected by the acute T. b. evansi infection whilst the spleen was more affected by the subacute T. b. brucei infection. Our results provide a number of possible reasons why mice infected with T. b. evansi die sooner than those infected with T. b. brucei: (1) mice infected with T. b. evansi may need more stress response proteins to help them pass through the infection and these are probably excessively consumed; (2) proliferating cell nuclear antigen was more down-regulated in the liver of mice infected with T. b. evansi, which indicated that the inhibition of proliferation of hepatocytes in mice infected with T. b. evansi might be more severe than that in T. b. brucei infection; and (3) more hepatocyte apoptosis occurred in the mice infected with T. b. evansi and this might be probably the most important reason why mice died sooner than those infected with T. b. brucei. Studies of the changes in the gene expression profile in the liver and spleen of mice infected with T. b. brucei may be helpful in understanding the mechanisms of pathogenesis in Nagana disease at the molecular level. By comparing the gene profiles of the liver and spleen of mice infected with T. b. brucei with T. b. evansi, we have identified a number of factors that could explain the differences in pathogenesis in mice infected with these two African trypanosomes.     

Free radical scavenging and radioprotective activity of dehydrozingerone against whole body gamma irradiation in Swiss albino mice

Dehydrozingerone (DZ) was explored for in vitro-in vivo antioxidant potential and in vivo radioprotective activity against whole body gamma irradiation in Swiss albino mice. DZ scavenged the ABTS (2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (1, 1-dipehnyl-2-picrylhydrazyl) free radicals at room temp. DZ reduced Fe (III) to Fe (II) at pH 7.4 and scavenged the NADH/phenazine methosulfate generated superoxide radical in cell free system. DZ also scavenged the nitric oxide radical generated by sodium nitroprusside. To evaluate the radioprotective activity, mice were exposed to whole body gamma irradiation 30 min after the drug treatment at a dose rate of 1.66 Gy/min. Pretreatment with DZ 75, 100 and 125 mg/kg, i.p. reduced the radiation induced mortality and increased the mean survival times (MSTs). An i.p. dose of DZ 100 mg/kg was found the most effective dose in preventing radiation sickness and increasing the MST. Pretreatment DZ100 mg/kg maintained the spleen index (spleen weight/body weight x 100) and stimulates the endogenous spleen colony forming units (CFU). Pretreatment with DZ100 mg/kg maintained the villus height close to normal, prevents mucosal erosion and basement membrane damage in irradiated mice jejunum. However, no significant reductions in dead, inflammatory and mitotic cells were observed in DZ pretreated mice, but there was an increased in crypt cells proliferation and regeneration. Pretreatment with DZ100 mg/kg significantly elevated the endogenous antioxidant enzymes (GSH, GST and SOD) in mice at 2, 4 and 8 h post sham irradiation. Radiation induced fall in endogenous antioxidant enzymes was significantly prevented by DZ pretreatment. Pretreatment with DZ 75 and 100 mg/kg reduced the radiation induced micronucleated polychromatic erythrocytes (MPCE) and normochromatic erythrocytes (MNCE) in mice bone marrow. DZ also maintained the polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) ratio (P/N ratio) in irradiated mice. Dose modifying factor (DMF) was calculated by using the graded radiation dose (8.0, 9.0, 9.5 and 10 Gy). DZ 100 mg/kg elevated radiation LD(50) from 9.1 to 10.0 Gy, indicating the DMF of 1.09.     

大鼠脾白髓交错突细胞和巨噬细胞的形态计量分析

本文应用形态计量学方法对脾白髓内Ｓ－１００蛋白阳性交错突细胞和ｌｙｓｏｚｙｍｅ阳性巨噬细胞的一些形态计量参数进行比较分析,结果如下：两种细胞相比,交错突细胞和巨噬细胞的平均面积无显著差异,而平均周长和平均形态因子在交错突细胞明显大于巨噬细胞（Ｐ＜０．０１）;在单位面积脾白髓内,交错突细胞的面数密度和面密度明显小于巨噬细胞的相应数值（Ｐ＜０．０１）,提示这两种细胞在形态计量方面也有明显区分。鉴于这些数值与其细胞的形态和数量密切相关,并随细胞的变化而产生相应的改变,因而是有意义的形态计量参数。     

内毒素所致SIRS/MODS小鼠脾细胞损伤的形态学观察

目的 应用大肠杆菌内毒素脂多糖（LPS）腹腔注射制备小鼠全身炎症反应综合片/多器官功能失常综合征（SIRS/MODS）模型。方法 用免疫组化的方法检测了Bcl-2的表达。结果 随LPS作用时间的延长,脾损伤逐渐加重,HE染色中,生发中心和动脉周围淋巴鞘分别在LPS注射后9小时和18小时出现大量深浅不一的颗粒状细胞碎片。TUNEL阳性染色细胞随时间延长而增多,电镜下可见到凋亡的淋巴细胞,在18小时还见到细胞坏死现象,Bcl-2的表达随着LPS作用时间的延长而明显下降,与TUNEL染色的相关分析表明,Bcl-2的表达与细胞凋亡有显著的负相关。结论 在LPS所致的SIRS/MODS模型中,脾细胞损伤以凋亡为主,随LPS作用时间延长而加重,在晚期还会出现细胞坏死。Bcl-2参与了LPS引起的脾细胞凋亡效应。     

羚牛(Budorcas taxicolor)部分脏器特点的观察

本文对2只羚牛的雌性生殖器官及肝、肾、脾等脏器进行了形态描述,并与黄牛及羊的相应器官进行了比较,为探讨羚牛的分类地位提供了解剖学资料。     

B lymphocyte differentiation in lethally irradiated and reconstituted mice

The recovery of the B lymphocyte compartments was investigated in lethally irradiated mice reconstituted with fetal liver cells. This was done by means of immunofluorescence on frozen sections of spleen, lymph nodes and Peyer's patches. The first B lymphocyte recovery in the spleen was observed on day 8, a few days earlier than in lymph nodes and Peyer's patches (day 13). These early B cells in the spleen were found in the central part of the periarteriolar lymphatic sheath (PALS). Later on, while increasing in number, the B cells formed growing follicles at the periphery of the PALS. Subsequently, brightly fluorescent B cells appeared in the marginal zone, which surrounded the follicles. Another two weeks later, around day 30, also germinal center formation was observed in the follicles of the spleen. B cell development in lymph nodes and Peyer's patches started somewhat later than in the spleen, but once started, the recovery of the different compartments was completed very fast. Germinal center reactions were found in lymph nodes and Peyer's patches already on day 25, and thus earlier than in the spleen, but later than the first occurrence of the strongly fluorescent cells in the marginal zone. Apparently, germinalcenter formation is not essential for the recovery of the population of brightly fluorescent B cells in the marginal zone after irradiation and reconstitution.     

The ontogenetic development of the follicular dendritic cell

Summary After intravenous injection of horseradish peroxidase (HRP)-anti-HRP complexes in 21-day-old rats, complex trapping occurs on reticulum cells, forming the stroma of primary follicles of spleens. After intravenous injection of the same complexes in young adult rats (48 days old), trapping occurs on characteristic follicular dendritic cells (FDCs) located in well-developed germinal centers. These results strongly suggest that the follicular dendritic cell originates from a reticulum cell.Abbreviations FDC follicular dendritic cell - FRC fibroblastic reticulum cells - HRP horseradish peroxidase - RC reticulum cell