The development of the human spleen

Summary Splenic tissue of human fetuses from the 14^th to the 24^th week of gestation (menstrual age) were investigated by light- and electron microscopy to describe the development of the red and white pulp in close relationship to the differentiation of the vascular tree. Special interest is focussed on the differentiation of the T-cell- and the B-cell regions and their specific stationary cells.The preliminary stage, here called the primary vascular reticulum, lasts up to the 14^th gestational week (gw). Numerous erythrocytes, normoblasts and macrophages are seen among a network of mesenchymal cells and argyrophilic fibers. Hematopoiesis, especially erythropoiesis, can be recognized.The characteristic organ structure becomes established during the subsequent transformation stage of the fetal spleen, beginning with the 15^th gw. Splenic lobules begin to form during the 15^th to 17^th gw. They consist of a central artery, surrounded by a sheath of lightly stained stationary cells which resemble myofibroblasts. At the periphery of these lobules the red pulp forms. Initially mobile cells are distributed throughout the reticulum. Soon they begin to accumulate in the venous sinuses, which develop from lacunae among the reticular network and come into contact with the venous system. The endothelial wall of these sinuses remains discontinuous, confirming the theory of the open vascularization of the spleen. The development of the larger veins is correlated with the differentiation of the splenic trabeculae.The development of the white pulp is correlated with the stage of lymphoid colonization within the spleen, beginning around the 18^th gw. An accumulation of lymphocytes around the central arteries can be recognized during the 19^th and 20^th gw. These lymphoid cells show morphological and immunohistochemical characteristics of T-precursor cells. Within the now assembling periarterial lymphoid sheath (PALS) a few precursors of interdigitating cells (IDC) are recognizable, giving evidence for the differentiation of the T-cell region.Around the 23^rd gw the assemblage of primary follicles is discernible at the periphery of the PALS. Precursors of the follicular dendritic reticulum cell (FDRC), the specific stationary cell of the B-cell region, have been recognized. This observation leads to the conclusion that the small primary follicles represent the beginning formation of the B-cell region.The significance of the vascular system for the differentiation of the specific splenic organization is discussed.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 111)The authors appreciate the contribution of human fetal material from Dr. von Hollweg and Dr. Körner from the Hospital Heidberg, Hamburg, and the excellent technical assistance of Mrs. H. Hansen, Mrs. I. Knauer, Mrs. M.v. Kolszynski, Mrs. J. Quitzau, Mrs. H. Siebke and Mrs. H. Waluk     

担子菌多糖及羊脾RNA对肿瘤的抑制与有关组织中cAMP含量关系的探讨

本文讨论了对带瘤小鼠注射香菇多糖、松口蘑多糖和羊脾RNA后,活体内有关组织中cAMP含量与抑瘤率之间的关系。 结果表明,上述活性物质不仅增强了机体免疫活性,同时亦促使机体内脾、瘤等组织的cAMP增高,此种增高,与抑瘤率成正相关。     

Pathogenesis of hemosiderosis in lemurs: Role of dietary iron,tannin, and ascorbic acid

Clinical disease associated with excess iron deposition (hemosiderosis) in the duodenum, liver, and spleen occurs in captive lemurs. In this report we review the occurrence of hemosiderosis and related disease in the Zoological Society of San Diego lemur collection; we then define and describe potential pathogenic factors with the goal of establishing rational husbandry methods to limit or prevent the disease. At the San Diego Zoo, all 49 lemurs necropsied since 1968 were hemosiderotic, the severity increasing with increasing age; liver and kidney disease were common. Our review of iron metabolism, current knowledge on the pathogenesis of hemosiderosis in humans, and the diets of captive and wild lemurs reveals several key dietary substances that may contribute to lemur hemosiderosis: iron, tannins, and ascorbic acid. In captivity, excess dietary iron (commercial monkey chow) and high levels of ascorbic acid (citrus fruits) lead to enhanced iron uptake and increased toxicity of stored iron due to free radical formation. In the wild, lemurs have an unusual preference for leaves, fruits, and bark high in tannin, a polyphenolic secondary plant compound that rapidly chelates iron, protein, and minerals in the gastrointestinal (GI) tract, preventing their absorption. These findings suggest that hemosiderosis in captive lemurs results from a diet high in iron, high in ascorbic acid, and lacking in tannin. Immediate correction of captive diets may limit hemosiderosis in lemurs in the future.     

The restoration of the T-lymphoid system of nude mice: lower efficiency of nonlymphoid, epithelial thymus grafts.

The T-cell deficiency of nude mice is due to an abnormal differentiation of the thymus epithelium; it can be persistently corrected by grafting a neonatal thymus. However, grafted adult thymuses or epithelial thymuses are not repopulated by large numbers of host-derived lymphocytes, as is the case when a whole neonatal thymus is grafted. Furthermore, the repopulation of the spleen and lymph nodes by T cells is less pronounced than after whole neonatal thymus transplantation, and the restoration of the reactivity to T-cell mitogens is irregular. Therefore, the integrity and the age of the thymus graft are important for a good restoration of the T-lymphoid system of congenitally athymic animals.     

Immunosuppressive properties of leukotriene D4 and E4 in vitro

Leukotrienes D₄ and E₄ whose physiological function has been associated with smooth muscle contraction, are demonstrated to be potent suppressors of immunocompetent cell function. In concentrations as low as 10^?12 M both leukotriene D₄ and E₄ can inhibit mitogen-induced lymphocyte transformation. Higher concentrations of leukotrienes E₄ and D₄ will inhibit appearance of antibody-forming cells in tissue culture. These data suggest another role for the leukotrienes in addition to their function as slow-reacting substances.     

大鼠实验性脾虚证胃粘膜内分泌细胞变化的免疫组织化学研究

用正常成年雄性Wistar大鼠53只,体重100～150g,分为正常对照组、实验性脾虚组、自然恢复组和四君子汤治疗组。取胃,固定于Bouin液。制成石蜡切片,进行(1)HE染色;(2)免疫组织化学染色,按Sternberger PAP法显示胃泌素细胞(G细胞)、生长抑素细胞(D细胞)和5-HT细胞。根据细胞的免疫反应程度,将细胞分为强阳性、中等阳性和弱阳性三级,每例动物计数三种细胞各1,000个,并计算各级细胞占的百分比;(3)从正常对照组,脾虚组随机选择各5例动物,对D细胞和G细胞进行显微分光光度计的定量测定;(4)由四组动物随机选择各5例,进行G细胞和D细胞密度及G/D细胞比值的测定。本文的观察表明:(1)脾虚组胃粘膜未见明显的组织学变化;(2)内分泌细胞:与对照组相比,脾虚组G细胞和5-HT细胞中,弱阳性细胞增多,表明分泌活动增强;D细胞弱阳性和中等阳性细胞减少,强阳性细胞增多,表明分泌释放减弱,合成增强。与自然恢复组比较,治疗组G细胞和D细胞的分泌活动接近于对照组;5-HT细胞无明显的恢复;(3)显微分光光度计的测定结果与光镜观察一致,脾虚组G细胞胃泌素反应物的含量低于对照组,D细胞内生长抑素反应物的含量高于对照组;(4)脾虚组G细胞密度低于对照组(P<0.01),D细胞密度略高于对照组,G/D细胞比值也低于对照组(P<0.01)。本文结果提示,脾虚证这些内分泌细胞的分泌活动出现异常,可能是导致消化功能紊乱的原因之一。经四君子汤治疗后,内分泌细胞的分泌活动接近于对照组,说明此药对脾虚证有一定的治疗作用。     

Trypanosoma cruzi: Responses by cells from infected mice to alloantigens

In unidirectional mixed lymphocyte cultures containing (as responders, stimulators, or regulators) spleen cells from mice infected with Trypanosoma cruzi, alloantigen responses were less than in cultures containing normal spleen cells only. Depletion of plastic adherent cells from infected spleen cells (stimulators or regulators) reversed their inhibitory effect on normal spleen cells (responders); removal of adherent responder cells and/or B lymphocytes did not alter the low alloantigen responses of normal spleen cells (stimulated by infected spleen cells) or infected spleen cells (stimulated by normal spleen cells). Infected spleen cells were effective in regulating mixed lymphocyte cultures only when added at the initiation of the culture. Serum from infected mice suppressed mixed lymphocyte cultures containing responder spleen cells syngeneic to the serum donor if added up to 24 hr after initiation of cultures, whereas the “suppressor serum” had to be present at the initiation of cultures when responder cells were allogeneic to the serum donor. Cultures of infected spleen cells (whole or macrophage enriched) produced a factor which was suppressive when added to mixed lymphocyte cultures containing syngeneic responder cells at initiation. It is proposed that the serum suppressor substance regulates cell-mediated immune responses directly by suppressing the response-potential of cells and indirectly by triggering the release of a factor from adherent splenic cells which induces a hyporesponsive state in T lymphocytes.     

Effect of acute sodium nitrite intoxication on some essential biometals in mouse spleen

Background and aimSodium nitrite (NaNO₂) is an inorganic salt with numerous applications in a variety of industries, as well as in medicine. Nevertheless, exposure to high levels of NaNO₂ is toxic for animals and humans. Sodium nitrite intoxication is shown to decrease the activity of major antioxidant defence enzymes which is dependent on the maintenance of specific ion equilibrium. The aim of the present study was to investigate the effect of acute NaNO₂ intoxication on the content of the essential metals iron (Fe), calcium (Ca) and zinc (Zn) in mouse spleen.MethodsMature male ICR mice were divided into four groups and subjected to acute NaNO₂ exposure by a single intraperitoneal injection of 120 mg/kg body weight. Animals in each group were sacrificed at certain time interval after treatment (1 h, 5 h, 1 day and 2 days). Spleens were excised and processed for atomic absorption spectrometry analysis of Fe, Ca and Zn content.ResultsAt the first hour after treatment, a decrease in Fe and Ca levels was observed. One day following NaNO₂ administration, Zn concentration reached its lowest value and Ca levels remained lower, compared to the untreated controls. In contrast, Fe concentration increased on the first and second day after treatment.ConclusionThe results of the present study demonstrate that acute NaNO₂ intoxication provokes changes in the endogenous levels of Fe, Ca and Zn in mouse spleen. These findings suggest disruption of the ionic balance and impact on the activity of antioxidant defence enzymes.     

Regulation of splenic contraction persists as a vestigial trait in white-blooded Antarctic fishes

In fishes, the spleen can function as an important reservoir for red blood cells (RBCs), which, following splenic contraction, may be released into the circulation to increase haematocrit during energy-demanding activities. This trait is particularly pronounced in red-blooded Antarctic fishes in which the spleen can sequester a large proportion of RBCs during rest, thereby reducing blood viscosity, which may serve as an adaptation to life in cold environments. In one species, Pagothenia borchgrevinki, it has previously been shown that splenic contraction primarily depends on cholinergic stimulation. The aim of the present study was to investigate the regulation of splenic contraction in five other Antarctic fish species, three red-blooded notothenioids (Dissostichus mawsoni Norman, 1937, Gobionotothen gibberifrons Lönnberg, 1905, Notothenia coriiceps Richardson 1844) and two white-blooded “icefish” (Chaenocephalus aceratus Lönnberg, 1906 and Champsocephalus gunnari Lönnberg, 1905), which lack haemoglobin and RBCs, but nevertheless possess a large spleen. In all species, splenic strips constricted in response to both cholinergic (carbachol) and adrenergic (adrenaline) agonists. Surprisingly, in the two species of icefish, the spleen responded with similar sensitivity to red-blooded species, despite contraction being of little obvious benefit for releasing RBCs into the circulation. Although the icefish lineage lost functional haemoglobin before diversifying over the past 7.8–4.8 millions of years, they retain the capacity to contract the spleen, likely as a vestige inherited from their red-blooded ancestors.     

四种护脾养胃类中药水提物抗氧化能力测定

以罗丹明B为显色剂,采用分光光度法测定了护脾养胃类方剂中常见的当归、五味子、黄芩、红枣等四种中药水提物对·OH的清除能力.实验表明:这些中药永提取物对·OH都具有较强的清除作用,呈现明显的量效关系,其中红枣的清除能力最强.据此评价了这四种中药水提取物抗氧化能力大小顺序为:红枣＞当归＞黄芩＞五味子.