Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation.
Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation.
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疟原虫疟原虫：阵发性相关的脂质介导白细胞聚集。
DOI：
10.1186/1475-2875-6-62
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发表时间：
2007-05-22
期刊：
影响因子：
3
通讯作者：
Carter, Richard
中科院分区：
文献类型：
--
作者：
Karunaweera, Nadira;Wanasekara, Deepani;Chandrasekharan, Vishvanath;Mendis, Kamini;Carter, Richard
阵发性发热是间日疟原虫感染的特征，与患者循环中分裂感染的红细胞破裂同时发生。本研究描述了在发作期间释放的寄生虫和宿主因子存在的情况下，在体外形成突出的白细胞聚集体。将未感染malaria-naïve供者的全血细胞与发作期间取的血浆或正常人血浆孵育作为对照，在显微镜下观察细胞涂片是否有白细胞聚集。参与介导白细胞聚集的血浆因子通过免疫耗竭和重建实验确定。此外，进行生化表征以确定发作期间血浆中活性成分的化学性质。当细胞在发作期间收集的血浆中孵育时，只能看到白细胞聚集物。免疫耗竭和重建实验表明，宿主细胞因子tnf - α、GM-CSF、IL-6和IL-10以及发作血浆的两种脂质组分构成了这一现象的必要和充分的介质。发作血浆的两种脂质成分推测可能是寄生虫的来源，一种是含磷脂的部分，另一种是含胆固醇和甘油三酯的部分。磷脂部分的活性取决于细胞因子的存在，而不像胆固醇/甘油三酯含有部分，在没有添加细胞因子的情况下，比磷脂部分更活跃。来自急性间日疟原虫感染的无免疫患者的发作血浆的生物活性被针对间日疟原虫或恶性疟原虫分裂体提取物的免疫血清中和。然而，针对间日疟原虫的免疫血清比针对恶性疟原虫的免疫血清更有效，这表明所涉及的寄生虫活性可能至少部分具有抗原特异性。白细胞聚集被认为与间日疟原虫感染的发作有关。这种现象是由血浆因子介导的，包括宿主来源的细胞因子和假定的寄生虫来源的脂质。发作性血浆中磷脂组分的特征与其他人描述的寄生虫来源的、诱导tnf的GPI部分的特征一致。然而，活性较高的胆固醇/甘油三酯(s)代表了一种新的疟疾毒素，这是一类与间日疟原虫疟疾发作相关的新型生物活性脂质。
Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum indicating that the parasite activity involved may be antigenically at least partially parasite species-specific. Leukocyte aggregation was identified as associated with paroxysms in P. vivax infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of P. vivax malaria.
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DOI：
10.1016/s0169-4758(00)01784-1
发表时间：
2000-10-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Anders, RF;Saul, A
通讯作者：
Saul, A
DOI：
10.1016/s0169-4758(98)01298-8
发表时间：
1998-09-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Fell, AH;Smith, NC
通讯作者：
Smith, NC
DOI：
10.4269/ajtmh.1998.58.204
发表时间：
1998-02-01
影响因子：
3.3
作者：
Karunaweera, ND;Carter, R;Mendis, KN
通讯作者：
Mendis, KN
DOI：
10.1080/00034983.1993.11812819
发表时间：
1993-12-01
影响因子：
--
作者：
KWIATKOWSKI, D
通讯作者：
KWIATKOWSKI, D
影响因子：
3.3
作者：
Carter, R;Wijesekera, SK;Mendis, KN
通讯作者：
Mendis, KN