疟原虫入侵红细胞的相关分子及其机制

疟原虫入侵宿主红细胞具有高度的种特异性,这些特异性的分子基础是疟原虫蛋白质与宿主红细胞表面蛋白质的相互作用.寻找参与疟原虫入侵红细胞的相关分子及其入侵机制是疟疾研究领域的热点.针对疟原虫不同种和虫株的实验研究并结合生物信息学分析结果表明:裂殖子表面蛋白、网织红细胞结合蛋白家族、红细胞结合蛋白家族以及动力蛋白等是参与疟原虫入侵红细胞的重要蛋白.该文对这方面的研究进展作了系统的综述,并阐述这些蛋白质在疟原虫入侵过程不同阶段中的作用.     

恶性疟原虫Pf332分子DBL、TM和WR功能区蛋白质的转运分析

目的分析恶性疟原虫Pf332分子的DBL、TM和WR3个功能区蛋白质在虫体内的表达和分布以及与肌动蛋白的结合情况，探讨其在感染红细胞内的转运过程及功能，为进一步研究疟原虫侵人机制及筛选红内期疫苗候选抗原提供理论依据。方法将构建融有GFP基因的恶性疟原虫Pf332分子的Pf332DBL-GFP、Pf332TM-GFP和Pf332WR-GFP重组质粒分别转染到3D7虫株恶性疟原虫，通过活体荧光实时观察DBL、TM和WR蛋白质表达及其在染虫红细胞内的分布，运用间接免疫荧光共定位方法观察蛋白质DBI-TM和WR与肌动蛋白的结合情况。结果转染试验表明，重组DBL-GFP、TM-GFP和WR-GFP基因能在虫体中正常表达蛋白质，该蛋白均分布在染虫红细胞的纳虫泡内，但未能转运到红细胞的胞浆内。间接免疫荧光共定位表明恶性疟原虫Pf332分子的DBL、TM和WR等3个功能区蛋白质均未与肌动蛋白（β-actin）结合。结论Pf332分子的DBL、TM和WR等3个功能区蛋白在单独表达后自身均不能发生跨膜反应，即不能通过虫体的纳虫泡膜。由此推测，Pf332分子在虫体内合成后很可能通过多个功能基团协同作用转运到红细胞膜部位。     

多糖与恶性疟原虫的分子致病机制

在恶性疟原虫与人体细胞相互作用的过程中,子孢子通过黏附肝内皮细胞受体侵入肝脏,裂殖子通过黏附红细胞表面受体侵入红细胞,感染红细胞利用其表面膜蛋白与人体重要器官的血管内皮细胞表面分子发生黏附,最终导致血流受阻。这些黏附过程均是虫体蛋白与宿主细胞表面带有负电荷的多糖分子相互作用的结果。本文对恶性疟原虫与人体细胞相互作用的分子机制作一综述。     

四种恶性疟原虫裂殖子蛋白的主要等位双态性与入侵红细胞的两种选择性途径无关

恶性疟原虫入侵红细胞是由裂殖子上的配体与红细胞上的受体相互作用所介导的,不同的恶性疟原虫虫株或克隆共有两种入侵红细胞的选择性途径。在红细胞表面至少有三种恶性疟原虫入侵的受体,血型糖蛋白A和B(gpA、gpB),以及一种尚未鉴定的胰肽酶敏感的分子“X”。与gpA作用的恶性疟原虫配体是红细胞结合抗原175(EBA-175)。     

恶性疟原虫成对体蛋白的分离

作者用同位素标记、分子杂交、免疫沉淀和SDS-聚丙烯酰胺凝胶电泳及免疫电子显微镜技术等多种实验手段,研究了存在于Wellcomo(Lagos)株的恶性疟原虫裂殖子的成对体中一个分子量为140,000的蛋白质,描述了该蛋白质的制备,纯化,鉴定及部分特性。作者从被寄生的红细胞的抽提物中通过单克隆抗体亲和层析方法提纯了该蛋白质。发现该蛋白质是在裂殖子的裂殖生殖阶段被合成的,抗恶性疟原虫的单克隆抗体61.3识     

恶性疟原虫侵入人红细胞中的一个疏水反应

据报道人体红细胞中的血型蛋白A对于恶性疟原虫裂殖子体外侵入红细胞具有强烈的抑制作用,如将N-乙酰基葡萄糖胺接到象牛血清白蛋白(BSA)这样的大分子载体上,它也能抑制疟原虫感染。另外,还发现被抽去外在糖基化组的唾液糖蛋白同完整无损的分子一样,阻止疟原虫侵入红细胞,这些现象说明了在这些抑制剂中可能是某个组分在起作用或经过某个特定反应。为了研究这些     

恶性疟原虫var基因家族与抗原变异研究进展

恶性疟原虫变异抗原基因(var基因)家族编码的恶性疟原虫红细胞膜蛋白1(PfEMP1)是介导恶性疟原虫抗原变异和红细胞黏附微血管的媒介。本文从恶性疟原虫抗原变异和致病性、感染红细胞表面变异分子的表达、var基因家族的基因结构、PfEMP1蛋白的黏附特性以及var基因家族的变异调控等方面对恶性疟原虫var基因家族与抗原变异的研究进行综述。     

冈比亚恶性疟患儿红细胞流动粘附机制

恶性疟原虫寄生的红细胞粘附于血管内皮细胞是恶性疟原虫致病的主要因素。因此,研究粘附的分子机制和流变学特征具有重要意义。 作者对冈比亚恶性疟患儿血中分离的有恶性疟原虫寄生的红细胞粘附特性进行了研究。使红细胞从覆盖有甲醛固定的人脐静脉内皮细胞(HUVEC)或血小板的载玻片上流     

与红细胞膜及细胞骨架相互作用的疟原虫蛋白质

感染疟原虫的红细胞膜表面存在源于疟原虫的某些蛋白质。这些蛋白质系由裂殖子侵入红细胞时滞留于红细胞膜上及由疟原虫在红细胞内生长发育过程中产生并通过某些机制转运到红细胞膜表面。这些蛋白质通称为疟原虫感染的红细胞骨架相关蛋白。本文对其来源、特性、功能及与红细胞膜的相互作用进行了探讨。     

生物素衍生物阻止恶性疟原虫诱导被感染红细胞开放新的膜通道

恶性疟原虫入侵红细胞后在纳虫泡内发育。纳虫泡膜虽然把红细胞胞浆与原虫分隔开来 ,但是仍允许小分子溶质和蛋白质通过。被恶性疟原虫感染的红细胞膜通透性增加 ,小分子的溶质 (单糖、核苷、氨基酸等 )可以进入红细胞内 ,以满足疟原虫发育的需要。已经有很多种关于疟原虫吸收途径的假说来说明感染红细胞增加摄入可溶性物质。由于通常被正常红细胞排斥的生物素衍生物(sulfo NHS LC biontin)能进入被感染的红细胞内 ,可利用生物素衍生物共价结合蛋白质 (生物素化 )来探索小分子溶质 (包括生物素衍生物 )进入红细胞的途径。生物素衍生物能进…     

Human cerebral malaria

Possible factors contributing to the development of cerebral malaria were discussed based on pathological changes in Burmese patients who died of cerebral malaria. Blockage of cerebral capillaries by Plasmodium falciparum infected erythrocytes appeared to be the principal cause of cerebral malaria. From electron microscopic results, it was concluded that knobs on infected erythrocytes acted as focal junctions which mediated adhesion to endothelial cells. The knobs are, therefore, important contributors to the blockage of the capillary lumen and ensuing pathological changes in cerebral tissues. Host cell molecules such as OKM5 and thrombospondin may function as endothelial cell surface receptors for the attachment of knobs of P. falciparum infected erythrocytes. Immunological events might also play a role in the pathogenesis of cerebral malaria. This was suggested by the presence of IgG, IgM, P. falciparum antigens, and knob proteins in the cerebral capillaries of the people with cerebral malaria. It will be important to assess the candidate malaria vaccines now in development not only for their efficacy in reducing parasitemia but for effects they may have on the sequestration of infected erythrocytes in the brain.     

Sharing of antigens between Plasmodium falciparum and Anopheles albimanus

The presence of common antigens between Plasmodium falciparum and Anopheles albimanus was demonstrated. Different groups of rabbits were immunized with: crude extract from female An. albimanus (EAaF), red blood cells infected with Plasmodium falciparum (EPfs), and the SPf66 synthetic malaria vaccine. The rabbit's polyclonal antibodies were evaluated by ELISA, Multiple Antigen Blot Assay (MABA), and immunoblotting. All extracts were immunogenic in rabbits according to these three techniques, when they were evaluated against the homologous antigens. Ten molecules were identified in female mosquitoes and also in P. falciparum antigens by the autologous sera. The electrophoretic pattern by SDS-PAGE was different for the three antigens evaluated. Cross-reactions between An. albimanus and P. falciparum were found by ELISA, MABA, and immunoblotting. Anti-P. falciparum and anti-SPf66 antibodies recognized ten and five components in the EAaF crude extract, respectively. Likewise, immune sera against female An. albimanus identified four molecules in the P. falciparum extract antigen. As far as we know, this is the first work that demonstrates shared antigens between anophelines and malaria parasites. This finding could be useful for diagnosis, vaccines, and the study of physiology of the immune response to malaria.     

Pulmonary manifestations of uncomplicated falciparum and vivax malaria: cough,small airways obstruction,impaired gas transfer,and increased pulmonary phagocytic activity

Despite recognition of acute respiratory distress syndrome in both falciparum and vivax malaria, disease-related changes in pulmonary function have not been defined, and underlying mechanisms are not well understood. Respiratory symptoms, pulmonary function, pulmonary phagocytic cell activity, and longitudinal changes were examined in 26 adults with uncomplicated falciparum, vivax, and ovale malaria after treatment. Self-limiting cough occurred in both falciparum (36%) and vivax or ovale (53%) malaria. In infection with each malaria species, admission measures of airflow and gas transfer were lower than predicted, and mean lung (99m)technetium-sulfur-colloid uptake was significantly increased. Changes were most evident in falciparum malaria, with treatment resulting in initial worsening of airflow obstruction and gas transfer. Altered pulmonary function in malaria is common and includes airflow obstruction, impaired ventilation, impaired gas transfer, and increased pulmonary phagocytic activity, and its occurrence in both vivax and falciparum malaria suggests that there may be common underlying inflammatory mechanisms.     

Occurrence of a common epitope in circumsporozoite proteins of Plasmodium falciparum isolated from different areas in Thailand

Fifteen isolates of P. falciparum sporozoites obtained from patients with acute falciparum malaria from various malaria endemic areas in Thailand were tested for the presence of a common antigenic determinant in their CS protein molecules. SDS-PAGE and Western blot analysis using MAB or human serum antibodies specific to the CS proteins of the parasites revealed a common epitope shared in the CS proteins of all strains of P. falciparum tested. However, the CS proteins exhibited M.W. variation when different strains of the parasites were compared. A similar result was obtained when the human serum antibodies were used. The present study clearly indicated the occurrence of the common epitope in phenotypically different CS proteins among isolates of P. falciparum sporozoites and supported the notion that antigens containing these repetitive epitopes could be used as the candidates for the sporozoite vaccine against P. falciparum infection.     

Evidence against immune haemolysis in falciparum malaria in Thailand

Evidence of immune mediated haemolysis was sought in 83 patients with P. falciparum malaria in eastern Thailand. Amongst 73 patients with uncomplicated infection 12 (16.4%) had a weakly positive direct antiglobulin test (DAT). The incidence in 32 children aged 8-16 years was similar to that in adults. Of 10 patients with cerebral malaria, six adults, all of whom were in unrousable coma, had a positive DAT. Erythrocyte-bound IgG1 accounted for the positive DAT in all cases; sensitization with complement or other IgG subclasses was not found. Patients with uncomplicated malaria had a median value of 70 IgG molecules per erythrocyte compared with 65 molecules per cell in 67 healthy controls. This difference was not statistically significant but could account for the lower incidence of a positive DAT in control subjects (4.5%). There was no correlation between the number of IgG molecules per cell and the degree of anaemia during the acute or convalescent phases of the infection. There is no evidence from this study that an immunohaemolytic process contributes to the anaemia of falciparum malaria in eastern Thailand.     

Circulating receptors implicated in the cyto-adherence occurring in severe Plasmodium falciparum malaria in Thailand

The kinetic profiles of soluble chondroitin-sulphate A (CSA), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin were investigated in 17 patients hospitalized with Plasmodium falciparum malaria. The aim was to see if these circulating adhesion molecules could be considered as markers for the severity of P. falciparum malaria. The levels of all the adhesion molecules were found to be higher in the sera from all the malaria cases, both severe and uncomplicated, than in those from uninfected controls. The elevation in plasma CSA, reported for the first time, was statistically very significant (P = 0.00001). However, when severe cases were compared with the uncomplicated, there were no significant differences in the level of any of the receptors except ICAM-1, which was highest in those with the severe disease (P = 0.01). The absence of any significant correlation between the plasma concentration of CSA and malaria severity indicates that this adhesion molecule could not be used to predict the severity of malaria, although its role in sequestration of the parasites in pregnant women is well established.     

Noncardiogenic pulmonary edema and pulmonary fibrosis in falciparum malaria

Noncardiogenic pulmonary edema is an uncommon but serious complication of falciparum malaria. A case of fatal noncardiogenic pulmonary edema complicating falciparum malaria is presented in which the unfavorable outcome resulted from rapidly developing pulmonary fibrosis, documented through open-lung biopsy. Possible mechanisms of lung injury in falciparum malaria include: impaired perfusion and tissue hypoxia in the pulmonary microcirculation caused by reduced effective circulating volume; abnormal autonomic effects on the lung resulting from reduced blood flow in the central nervous system; immunologic injury to alveolar-capillary structures; and morphologic changes in the surface membranes of infected erythrocytes leading to sequestration of parasitized erythrocytes in vascular beds and pulmonary capillary damage. That pulmonary involvement in falciparum malaria is usually associated with high-grade parasitemia, concurrent cerebral involvement, and delay in institution of antimalarial therapy emphasizes the importance of early diagnosis and treatment.     

Antimalarial drug resistance of Plasmodium falciparum in India: changes over time and space

After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965. However, the initial success could not be maintained and a resurgence of malaria began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was first reported in 1973 and increases in antimalarial resistance, along with rapid urbanisation and labour migration, complicated the challenge that India's large geographical area and population size already pose for malaria control. Although several institutions have done drug-resistance monitoring in India, a complete analysis of countrywide data across institutions does not exist. We did a systematic review of P falciparum malaria drug-efficacy studies in India to summarise drug-resistance data and describe changes over the past 30 years to inform future policy. Continued use of chloroquine for treatment of P falciparum malaria in India will likely be ineffective. Resistance to sulfa-pyrimethamine should be closely monitored to protect the effectiveness of treatment with artesunate plus sulfadoxine-pyrimethamine, which is the new first-line treatment for P falciparum malaria. Strategies to reduce the emergence and spread of future drug resistance need to be proactive and supported by intensive monitoring.     

Fighting malaria with engineered symbiotic bacteria from vector mosquitoes

The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)(4), four copies of Plasmodium enolase-plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria.     

2008-201年南京市输入性恶性疟疫情

目的 目的 了解南京市输入性恶性疟疫情, 为制定疟疾防控措施提供依据。方法 方法 统计2008-2012年全市输入性恶 性疟疫情资料, 结合流行病学调查进行描述性分析。结果 结果 2008-2012年, 南京市共报告58例输入性恶性疟病例, 逐年分 别为3、 5、 15、 17、 18例, 呈逐年增多趋势, 其中94.8%的病例为从非洲疟疾流行区回国人员。2012年输入性恶性疟病例占 全市报告病例的81.2%。结论 结论 南京市输入性恶性疟逐年增多, 应加强监测与防控。