High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria.

High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria.
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DOI:
10.1371/journal.pone.0084181
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Dodoo D
Dodoo D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Adukpo S;Kusi KA;Ofori MF;Tetteh JK;Amoako-Sakyi D;Goka BQ;Adjei GO;Edoh DA;Akanmori BD;Gyan BA;Dodoo D

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脑型疟疾 (CM) 是撒哈拉以南非洲儿童大部分与疟疾相关的死亡的原因。尽管尚不清楚,但 CM 的发病机制涉及寄生虫和宿主因素,这些因素通过细胞粘附到血管内皮来促进寄生虫的隔离。脑微血管系统的细胞粘附被认为涉及宿主内皮受体 CD54 或细胞间粘附分子 (ICAM)-1,而其他受体(例如 CD36)通常参与其他器官中寄生虫的细胞粘附。因此,我们研究了宿主 ICAM-1 表达和寄生虫上针对 ICAM-1 结合变异表面抗原 (VSA) 的抗体水平对 CM 发展的贡献。招募 0.5 至 13 岁的儿科疟疾患者,并根据明确的标准分为 CM 和无并发症的疟疾 (UM) 患者。使用标准化 ELISA 方案测量急性血浆样本中的可溶性 ICAM-1 (sICAM-1) 水平。在急性和恢复期状态下,通过流式细胞术测量 CD36 或 ICAM-1 结合 VSA 的 IgG 水平。用于比较各组的 Wilcoxon 符号等级检验分析揭示了 sICAM-1 水平与 CM 之间的关联 (p<0.0037)。两组患者入院时和治疗开始后 7 天的 CD36 结合 VSA 抗体中位水平相当 (p>0.05)。任何患者组内急性期和恢复期样本中 CD36 结合 VSA 的抗体中位水平也相当。然而,两组患者入院时 ICAM-1 结合 VSA 的抗体中位水平均显着低于恢复期间。高水平的 sICAM-1 与 CM 相关,并且 sICAM-1 水平可能反映膜结合形式的表达水平。与 CD36 结合寄生虫的抗体相比,针对 ICAM 结合寄生虫的抗 VSA 抗体水平与 UM 和 CM 的相关性更强。因此,宿主 sICAM-1 水平的增加与 CM 相关,而表达非 ICAM-1 结合 VSA 的寄生虫抗体则不然。
Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM. Paediatric malaria patients, 0.5 to 13 years were recruited and grouped into CM and uncomplicated malaria (UM) patients, based on well defined criteria. Standardized ELISA protocol was used to measure soluble ICAM-1 (sICAM-1) levels from acute plasma samples. Levels of IgG to CD36- or ICAM-1-binding VSA were measured by flow cytometry during acute and convalescent states. Wilcoxon sign rank-test analysis to compare groups revealed association between sICAM-1 levels and CM (p<0.0037). Median levels of antibodies to CD36-binding VSA were comparable in the two groups at the time of admission and 7 days after treatment was initiated (p>0.05). Median levels of antibodies to CD36-binding VSAs were also comparable between acute and convalescent samples within any patient group. Median levels of antibodies to ICAM-1-binding VSAs were however significantly lower at admission time than during recovery in both groups. High levels of sICAM-1 were associated with CM, and the sICAM-1 levels may reflect expression levels of the membrane bound form. Anti-VSA antibody levels to ICAM-binding parasites was more strongly associated with both UM and CM than antibodies to CD36 binding parasites. Thus, increasing host sICAM-1 levels were associated with CM whilst antibodies to parasite expressing non-ICAM-1-binding VSAs were not.
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