TLR与足细胞损伤

TLRs是一类重要的模式识别受体家族,主要调节天然免疫反应.研究发现在肾脏固有细胞及间质细胞都有TLR表达,其介导的炎症反应参与了许多肾脏疾病的发生.多种足细胞标志蛋白的发现加快了足细胞表面分子的研究进程.目前已发现足细胞表面有TLR的表达,且TLR的表达与足细胞的损伤有关.文章综述了已经发现的TLR成员及其与足细胞损...     

TLR4在心肌缺血再灌注损伤中作用的研究进展

急性心肌梗死(acute myocardial infarction, AMI)是全球范围内导致高致残率和高死亡率的主要疾病。对于AMI患者,及时、有效的再灌注治疗对减少心肌梗死面积、挽救生命至关重要,目前临床上采用的再灌注治疗方法主要是溶栓治疗和经皮冠状动脉介入治疗(percutaneous coronary intervention, PCI)。但是,心肌再灌注可以导致其缺血再灌注(ischemia/reperfusion, I/R)损伤,包括心肌细胞死亡、梗死面积增大、左室收缩功能障碍等,该损伤的发生机制和治疗策略仍在研究中。越来越多的实验研究表明,固有免疫的成员之一TLR可能通过多条信号通路在I/R损伤中起关键作用。文章主要针对TLR4在心肌I/R损伤中作用的研究进展作一综述。     

地塞米松对小鼠脾脏巨噬细胞内TLR4和TLR2表达的影响

为观察小鼠脾巨噬细胞内的TLR4和TLR2在脂多糖 (LPS )刺激后 ,地塞米松 (Dx )对其表达量的影响 ,在向BALB/c小鼠腹腔内注射LPS和Dx后采用贴壁法分离小鼠脾巨噬细胞 ,通过半定量RT PCR方法测定了TLR4和TLR2mRNA的表达量。结果显示 :①LPS刺激后 ,小鼠脾巨噬细胞内TLR4mRNA显著上调 (吸光度比为 0 11) ,TLR2上调不明显 (吸光度比为0 0 0 8) ;②预先注射不同剂量Dx ,分别为 0 1mg/kg、 1mg/kg、 10mg/kg ,再用LPS刺激小鼠。注射了Dx后巨噬细胞TLR4mRNA表达量较单纯注射LPS的小鼠显著降低 (吸光度比分别为 0 0 93、 0 0 5 0和 0 0 14 ) ;但TLR2mRNA表达量随着Dx使用剂量增加而增加 (吸光度比分别为 0 0 5 4、 0 0 80和 0 16 1)。该项研究表明TLR4是参与LPS引起炎症反应的主要Toll样受体 ,而TLR2不起主要作用 ;Dx对LPS刺激后TLR 4mRNA的表达有抑制作用 ,而对TLR2mRNA的表达有增强作用 ;Dx抑制LPS引起的炎症反应可能与抑制TLR4的表达有关     

TLR家族在中枢神经系统中的免疫调节作用

Toll样受体（Toll—like receptors，TLRs）家族识别病原体相关分子模式（PAMPs）从而启动固有免疫应答，属于模式识别受体（PRRs）。目前关于TLRs在中枢神经系统中发挥的免疫调节作用所进行的研究已经积累了一些资料。深入探讨TLR家族在中枢系统的慢性炎症中的作用，将有助于揭示阿尔茨海默病等常见病的发病机理及寻求其防治新措施。     

TLR4及内源性配体对缺血-再灌注损伤的作用

Toll样受体4(TLR4)在内源性配体参与下介导缺血再灌注损伤,两者的结合对组织损伤和固有免疫应答起重要作用。肝、肾、肺、脑等发生缺血再灌注损伤早期，细胞释放各种内源性配体，被TLR4 识别并结合。Toll样受体4与内源性配体(如HMGB1)的结合可能是缺血再灌注损伤中最主要的炎症应答的触发器，并引起一系列导致炎症和免疫应答的级联反应。阻断两者的结合可能对各种缺血-再灌注损伤引起的炎症反应和细胞损伤有保护作用。     

TLR2及TLR4在侵袭性肺曲霉病小鼠中的表达

目的 研究Toll样受体(TLR)2和TLR4在侵袭性肺曲霉病小鼠中的表达,探讨TLR2和TLR4在侵袭性肺曲霉病中的作用. 方法 将小鼠分为3组:A组为正常对照组;B组为未免疫抑制但感染烟曲霉菌组;c组为侵袭性肺曲霉病(IPA)模型组,给予免疫抑制并感染烟曲霉菌.在感染后8、24、48和72 h时相点,处死小鼠,取肺组织,采用组织病理学方法观察肺组织的病理损伤,RT-PCR法检测肺组织各个时相点的TLR2、TLR4、TNF.ot和β-tublin的表达.TLR2、TLR4、TNF-α的PCR产物电泳条带的扫描密度值与同时扩增的β-tublin电泳条带的扫描密度值的比值用以表示TLR2、TLR4和TNF-α的相对表达水平. 结果 病理观察结果显示,对照组小鼠的肺组织结构正常;正常小鼠感染烟曲霉菌后,小鼠的肺组织有炎症细胞浸润、出血等炎症反应,但未见孢子萌芽生成菌丝;而IPA模型小鼠的肺组织病理损伤严重,可见炎症细胞浸润、肺泡塌陷伴随出血,孢子聚积并萌芽生成菌丝.8、24、48 h 3个时间点的TLR4和24、48 h两个时相点的TNF-α在IPA模型小鼠肺组织中的表达要低于烟曲霉菌感染的正常小鼠(P<0.05),而TLR2在烟曲霉菌感染的正常小鼠和IPA模型小鼠肺组织中呈现低表达,但24、72 h时相点的TLR2在IPA模型小鼠的表达要低于烟曲霉菌感染的正常小鼠(P<0.05). 结论 TLR4及其下游分子TNF-α在IPA模型小鼠肺组织中低表达,在组织病理镜检中可见肺曲霉病典型肺组织病理损伤和孢子生成菌丝.     

TLR2和TLR4在原发性肝癌中的表达

目的：本研究通过检测原发性肝癌Toll样受体2（TLR2）和Toll样受体4（TLR4）的表达，分析其与临床病理生理因素的关系，探讨TLR2，TLR4在原发性肝癌疾病过程中的可能作用。方法：采用免疫组化法和实时荧光定量PCR分别在蛋白水平及mRNA水平检测原发性肝癌组织和配对癌旁组织TLR2、TLR4的表达。结果：原发性肝癌组织在蛋白水平和mRNA水平TLR2和TLR4的表达均明显低于癌旁组织（P<0.01）。但免疫组化结果显示不论是肝癌组织还是癌旁组织，TLR2和TLR4的表达均明显高于正常肝组织（P<0.01，P<0.05），有门静脉分支癌栓的患者癌组织TLR4的表达强度低于无门静脉分支癌栓的患者（P<0.05）。结论：肝癌组织TLR2和TLR4的表达与癌旁组织相比受到相对抑制，但高于正常肝组织，TLR2和TLR4信号途径可能参与了原发性肝癌的病理过程。     

Toll样受体4在肺缺血再灌注损伤免疫机制调控中作用

肺缺血再灌注损伤(LIRI)是肺移植术后一种严重威胁生命安全的并发症,并且与随后的闭塞性细支气管炎综合征的发展密切关联.当细胞受损时,其通过Toll样受体家族(TLRs)尤其是Toll样受体4(TLR4)来识别所释放的内源性配体,这一过程即为损伤关联分子模式(DAMPs).研究表明,TLR4在肺缺血再灌注损伤的病理生理过程中担任重要角色.     

TLR2和TLR4在人慢性根尖周病组织肥大细胞上的表达

 目的: 观察人不同类型慢性根尖周病组织中肥大细胞(mast cells,MCs)上Toll样受体2(Toll-like receptor 2,TLR2)和TLR4的表达情况,探讨TLR2-类胰蛋白酶(tryptase)和TLR4-tryptase双阳性MCs在慢性根尖周疾病发病机制中的作用。方法: 将60例自愿参与本研究的受试者按根尖周病分类标准分为3组:(1)正常对照组;(2)根尖周肉芽肿组;(3)根尖周囊肿组。将根尖周组织标本置于4%甲醛固定液中浸泡48 h以上,制作连续组织切片。HE染色,光学显微镜下观察各组根尖周标本的组织学变化;免疫荧光双染色后于荧光显微镜下观察TLR2-tryptase和TLR4-tryptase双阳性MCs在根尖周组织中的分布情况。结果: 根尖周病变组TLR2-tryptase和TLR4-tryptase双阳性MCs比正常牙周膜组明显增多(P<0.01);与根尖肉芽肿组相比,根尖囊肿组TLR2-tryptase及TLR4-tryptase双阳性MCs数目明显增高(P<0.01)。结论: TLR2及TLR4在慢性根尖周疾病组织中MCs上表达增加,提示TLR2-tryptase及TLR4-tryptase双阳性MCs可能参与慢性根尖周病发病过程的免疫调节。     

TLR4信号转导通路在肿瘤中的作用

慢性炎症与恶性肿瘤密切相关,Toll样受体4(TLR4)在肿瘤中的广泛表达提示其在慢性炎症致瘤机制中发挥重要作用.活化肿瘤细胞TLR4不仅促进肿瘤的生成和转移,而且参与肿瘤的免疫逃逸.另一方面,免疫佐剂又通过激活免疫细胞的TLR4信号产生抗肿瘤免疫.因此,TLR4在肿瘤中起着双刃剑的作用.     

Parasitic diseases of the central nervous system

Parasitic infections, though endemic to certain regions, have over time appeared in places far removed from their original sites of occurrence facilitated probably by the increase in world travel and the increasing migration of people from their native lands to other, often distant, countries. The frequency of occurrence of some of these diseases has also changed based on a variety of factors, including the presence of intermediate hosts, geographic locations, and climate. One factor that has significantly altered the epidemiology of parasitic diseases within the central nervous system (CNS) is the HIV pandemic. In this review of the pathology of parasitic infections that affect the CNS, each parasite is discussed in the sequence of epidemiology, life cycle, pathogenesis, and pathology.     

Rhabdoid tumours of the central nervous system

Summary Three cases of rhabdoid tumour of the central nervous system arising in a supratentorial location are reported. The patients were 18, 14, and 7 years old. All three tumours showed a common morphology. The neoplastic cells were usually globoid with round nuclei and prominent nucleoli and large acidophilic, cytoplasmic inclusions were present in many of them. These inclusions showed strong immunoreactivity for vimentin, weak immunoreactivity for epithelial membrane antigen and focal immunoreactivity for cytokeratins. Ultrastructurally they were made up of whorls of intermediate filaments, 8–10 nm in thickness. Rhabdoid tumours of the central nervous system, whatever the cell of origin, appear to be an independent entity with identifiable histology and aggressive behaviour.     

Stem cell-based cell replacement strategies for the central nervous system

During human development, cells of the blastocyst inner cell mass proliferate and give rise to each cell in the human body. It is that potential which focuses intense interest on these stem cells as a substrate for cell-based regenerative medicine. An increased understanding of the interrelation of processes that govern the formation of various cell types will allow for the directed differentiation of stem cells into specified cells or tissues that can ameliorate the effects of disease or damage. Perhaps the most difficult cells and tissues to derive for use in cell replacement strategies are the diverse neurons, glia and complex networks of the central nervous system (CNS). Here we present emerging perspectives on the development of neuronal and glial cells from stem cells for clinical application to CNS diseases and injury.     

Lack of Toll-like receptor 4 and 2 polymorphisms in Korean patients with bacteremia

Toll-like receptors (TLRs) are pattern-recognition receptors that are important in innate immune responses to bacterial infection. The purpose of this study is to describe the prevalence of TLRs genetic variations in the bacteremic patients in Korea. A total of 154 patients with bacteremia and 179 healthy volunteers were included. The Asp299Gly and Thr399Ile allele of the TLR4 gene and Arg753Gln and Arg677Trp allele of the TLR2 gene were tested by PCR-RFLP. The DNA sequences were determined to confirm the PCR-RFLP results. Contrary to the expectation, no genetic polymorphisms were detected in both groups of this study, suggesting that it is very rare in Korean.     

Microvascularization of the human central and peripheral nervous system: A new microcomputed tomography method

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Inflammatory pseudotumors of the central nervous system

Inflammatory pseudotumor is a disease with unsettled pathogenesis. The brain is a rare site of occurrence. The aim of this study is to investigate ALK-1 protein expression and IgG4-positive plasma cells detection in 4 intracranial inflammatory pseudotumors. Three dural-based and 1 intraventricular inflammatory pseudotumors were retrieved from the hospitals' archive. The data on clinical presentation, radiological findings, procedure undertaken, and patients' progress were collected. Sections from the excised lesions were examined under hematoxylin and eosin, histochemical, and immunohistochemical staining including ALK-1 and IgG4. All 4 cases displayed typical histological features of inflammatory pseudotumor with dense lymphoplasmacytic infiltrate admixed with small number of benign-looking spindle cells in a collagenous stroma. Three cases exhibited high density of IgG4-positive plasma cells per high-power field. ALK-1 was negative. ALK expression was not found in any of our cases. On the contrary, the detection of significant number of IgG4-positive plasma cells in 3 inflammatory pseudotumors suggests that a considerable proportion of intracranial inflammatory pseudotumor may belong to the IgG4-related subgroup. Hence, a trial of corticosteroid after histological confirmation may be valid to avoid unnecessary risk-taking neurosurgical procedures or in cases with incomplete tumor removal.     

哮喘豚鼠结状神经节,脊神经节和中枢内神经激肽A含量变化

应用放射免疫分析方法，检测16只哮喘豚鼠一级传入系统和中枢内神经激肽A（NKA）的水平。与正常对照组（结状神经节62．82±11.09pg/gw.w，C7～C8段脊神经节53．78±12．63，T1～T2段脊神经节54．23±19．08，T3~T5段脊神经节50．53±14．23pg／gw．w;C7～T5段脊髓后角45．86±19．56，孤束核55．27±19．68pg/gw．w．和延髓腹侧浅层37.36±18．29pg/gw．w．）相比，哮喘豚鼠一级传入系统和中枢内（结状神经节83．81±15．23pg/gw．w．C7～C8段脊神经节72．11±17．16．T1～T2段脊神经节73．95±23．76，T3～T5段脊神经节70.53±14．23pg／gw．w，C7~T5段脊髓后角60.25±21．38pg／gww．孤束核71．36±18．76pg／gw．w和延髓腹侧线层49．58±20．19pg／gw．w．）NKA水平明显升高（P＜0．05）．这些结果提示，一级传入系统和中枢内的NKA可能参与哮喘的发病机制。     

Selective central nervous system tropism of primary central nervous system lymphoma

Primary Central nervous system lymphoma (PCNSL) is most frequently a diffuse large B cell lymphoma (DLBCL), which is confined to the Central nervous system (CNS). We performed an experiment in which lymphoma cells from a PCNSL patient were implanted subcutaneously in an athymic mouse. The lymphoma cells were shown to home to the CNS with histologic evaluations of the brain showing multiple large B cells in blood vessels consistent with intravascular large B cell lymphoma (IVL). We did not find any evidence of lymphoma at the site of implantation or other locations. The findings are consistent with highly selective tropism of PCNSLforthe CNS and its vasculature.