Laboratório de Pesquisas em Malária, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2011 Aug;106 Suppl 1:34-43. doi: 10.1590/s0074-02762011000900005.
The glutamate-rich protein (GLURP) is an exoantigen expressed in all stages of the Plasmodium falciparum life cycle in humans. Anti-GLURP antibodies can inhibit parasite growth in the presence of monocytes via antibody-dependent cellular inhibition (ADCI), and a major parasite-inhibitory region has been found in the N-terminal R0 region of the protein. Herein, we describe the antiplasmodial activity of anti-GLURP antibodies present in the sera from individuals naturally exposed to malaria in a Brazilian malaria-endemic area. The anti-R0 antibodies showed a potent inhibitory effect on the growth of P. falciparum in vitro, both in the presence (ADCI) and absence (GI) of monocytes. The inhibitory effect on parasite growth was comparable to the effect of IgGs purified from pooled sera from hyperimmune African individuals. Interestingly, in the ADCI test, higher levels of tumour necrosis factor alpha (TNF-α) were observed in the supernatant from cultures with higher parasitemias. Our data suggest that the antibody response induced by GLURP-R0 in naturally exposed individuals may have an important role in controlling parasitemia because these antibodies are able to inhibit the in vitro growth of P. falciparum with or without the cooperation from monocytes. Our results also indicate that TNF-α may not be relevant for the inhibitory effect on P. falciparum in vitro growth.
谷氨酸丰富蛋白(GLURP)是一种在人类疟原虫生命周期的所有阶段都表达的外抗原。抗-GLURP 抗体可以通过抗体依赖性细胞抑制(ADCI)在单核细胞存在的情况下抑制寄生虫的生长,并且在蛋白质的 N 端 R0 区域已经发现了一个主要的寄生虫抑制区域。在此,我们描述了在巴西疟疾流行地区自然接触疟疾的个体血清中存在的抗-GLURP 抗体的抗疟原虫活性。抗-R0 抗体在体外对 P. falciparum 的生长表现出强大的抑制作用,无论是在单核细胞存在(ADCI)还是不存在(GI)的情况下。这种对寄生虫生长的抑制作用与从高免疫的非洲个体的混合血清中纯化的 IgG 的作用相当。有趣的是,在 ADCI 测试中,在寄生虫血症较高的培养物上清液中观察到更高水平的肿瘤坏死因子 alpha(TNF-α)。我们的数据表明,GLURP-R0 在自然暴露个体中诱导的抗体反应可能在控制寄生虫血症方面发挥重要作用,因为这些抗体能够在没有单核细胞合作的情况下抑制 P. falciparum 的体外生长。我们的结果还表明,TNF-α可能与体外生长的 P. falciparum 抑制作用无关。