The schistosome oesophageal gland: initiator of blood processing.

The schistosome oesophageal gland: initiator of blood processing.
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DOI:
10.1371/journal.pntd.0002337
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发表时间:
2013
影响因子:
3.8
通讯作者:
Wilson RA
Wilson RA
中科院分区:
医学2区
文献类型:
--
作者:
Li XH;de Castro-Borges W;Parker-Manuel S;Vance GM;Demarco R;Neves LX;Evans GJ;Wilson RA

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尽管血吸虫食管腺的超微结构在​​ 35 年前就已被描述,但其在处理摄入的血液中的作用从未确定。目前的研究是由我们对腺体中 MEG-4.1 表达的鉴定以及对后食管中红细胞脱壳的观察而促成的。后食管的显着特征,通过共聚焦和电子显微镜观察,是由内衬合胞体的板状延伸和基底内陷提供的膜表面积的巨大增加,以及独特的晶体囊泡在板之间释放其内容物。视频显微镜显示喂养过程分为两个阶段,血液首先积聚在前腔中,然后作为团块传递到后腔。在那里,它围绕着一块材料流动,通过共聚焦显微镜显示为束缚的白细胞。它们的数量远远超过根据管腔体积预测的数量,并且处于不同的损坏和破坏状态。在前食管中检测到完整的红细胞,但此后没有观察到,这意味着它们在进入后食管时迅速发生溶解。另外两个基因,MEG 4.2 和 14,被证明只在食管腺中表达。生物信息学预测 MEG 4.1 和 4.2 拥有一个带有共享基序的共同疏水区域,而 SjMEG-4.1 的抗体显示它与食管腔中的白细胞结合。还预测 MEG 4.1 和 14 被严重 O-糖基化,并且前者通过 2D 电泳和蛋白质印迹证实了这一点。食管腺及其产物在处理摄入的血液中起着核心作用。食管腔中宿主抗体的结合表明某些成分是抗体靶标,可以提供候选疫苗的新来源。血液中的成虫血吸虫摄入的宿主血液,通过短食道到达肠道,在那里其成分发生蛋白水解。食管腺包围食管的后半部,其膜表面积极大地扩展成板,这对其功能至关重要。腺体中产生的独特晶体囊泡的内容物被释放到管腔中并积聚在板之间。传入的宿主白细胞被束缚在后食管的管腔中并在那里受损或被破坏。红细胞进入后食管时也会被裂解。我们已经鉴定了腺体的另外两种蛋白质产物,以添加到我们之前描述的两种蛋白质产物中,它们可能与传入的宿主细胞相互作用以确定它们的命运。最后,我们证明来自受感染宿主的抗体可以识别并结合食管腺分泌物。这提出了腺体成分可能作为治疗性和预防性疫苗候选物的新来源的可能性。
Although the ultrastructure of the schistosome esophageal gland was described >35 years ago, its role in the processing of ingested blood has never been established. The current study was prompted by our identification of MEG-4.1 expression in the gland and the observation of erythrocyte uncoating in the posterior esophagus. The salient feature of the posterior esophagus, characterized by confocal and electron microscopy, is the enormous increase in membrane surface area provided by the plate-like extensions and basal invaginations of the lining syncytium, with unique crystalloid vesicles releasing their contents between the plates. The feeding process was shown by video microscopy to be divided into two phases, blood first accumulating in the anterior lumen before passing as a bolus to the posterior. There it streamed around a plug of material revealed by confocal microscopy as tethered leucocytes. These were present in far larger numbers than predicted from the volume of the lumen, and in varying states of damage and destruction. Intact erythrocytes were detected in the anterior esophagus but not observed thereafter, implying that their lysis occurred rapidly as they enter the posterior. Two further genes, MEGs 4.2 and 14, were shown to be expressed exclusively in the esophageal gland. Bioinformatics predicted that MEGs 4.1 and 4.2 possessed a common hydrophobic region with a shared motif, while antibodies to SjMEG-4.1 showed it was bound to leucocytes in the esophageal lumen. It was also predicted that MEGs 4.1 and 14 were heavily O-glycosylated and this was confirmed for the former by 2D-electrophoresis and Western blotting. The esophageal gland and its products play a central role in the processing of ingested blood. The binding of host antibodies in the esophageal lumen shows that some constituents are antibody targets and could provide a new source of vaccine candidates. Host blood ingested by adult schistosomes resident in the bloodstream, passes down a short esophagus to reach the gut where proteolysis of its constituents occurs. The esophageal gland surrounds the posterior half of the esophagus, which has a membrane surface area enormously expanded into plates that must be crucial for its functioning. The contents of a unique crystalloid vesicle, manufactured in the gland, are released into the lumen and accumulate between the plates. Incoming host leucocytes are tethered in the lumen of the posterior esophagus and damaged or destroyed there. Erythrocytes are also lysed as they enter the posterior esophagus. We have identified two further protein products of the gland, to add to the two we previously described, which may potentially interact with the incoming host cells to determine their fate. Finally, we have shown the antibodies from infected hosts can recognise and bind to the esophageal gland secretions. This raises the possibility that gland constituents may serve as a new source of candidates for both a therapeutic and prophylactic vaccine.
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发表时间: 2000-08-01
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影响因子: 2.4
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