DIRECT LYSIS OF TRYPANOSOMA-CRUZI - A NOVEL EFFECTOR MECHANISM OF PROTECTION MEDIATED BY HUMAN ANTI-GAL ANTIBODIES

DIRECT LYSIS OF TRYPANOSOMA-CRUZI - A NOVEL EFFECTOR MECHANISM OF PROTECTION MEDIATED BY HUMAN ANTI-GAL ANTIBODIES
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DOI:
10.1111/j.1365-3024.1991.tb00288.x
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发表时间:
1991-07-01
影响因子:
2.2
通讯作者:
BRENER, Z
BRENER, Z
中科院分区:
医学4区
文献类型:
--
作者:
GAZZINELLI, RT;PEREIRA, MES;BRENER, Z

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针对小鼠层粘连蛋白(半乳糖α-1-3半乳糖)中碳水化合物表位的抗GAL抗体,并在恰加斯病急性期患者的血清中检测到高水平的抗GAL抗体,导致克氏锥虫血型的直接裂解(DL),而不依赖于经典或替代的补体途径。此外,欧洲卫矛凝集素(EE)对半乳糖半乳糖α-1-3半乳糖具有相似的裂解活性,在相同浓度的纯化的抗半乳糖抗体中也表现出类似的裂解活性。用其他几种凝集素检测了DL的活性,但α-D-甘露糖和α-D-葡萄糖特异的刀豆蛋白A(ConA)也表现出裂解活性。凝集素和抗GAL抗体的裂解活性可以被特定的碳水化合物抑制,这表明这种现象与这些凝集素或抗GAL抗体与克鲁兹毛滴虫关键表面成分结合的能力有关。此外,克氏毛滴虫血型对小鼠的感染性可通过与急性查格斯病血清(ACS)孵育而明显灭活,但不能被免疫亲和层析吸附的ACS灭活,这有力地证明了高水平的抗GAL抗体参与了查格斯病原虫血症从急性到慢性期的下降。
Anti-gal antibodies directed against a carbohydrate epitope present in mouse laminin (galactosyl alpha-1-3 galactose) and detected in high levels in sera from patients in the acute phase of Chagas disease are responsible for the direct lysis (DL) of Trypanosoma cruzi blood forms independent of either the classic or alternative complement pathways. Furthermore, the lectins Euonymus europaeus (EE) specific for the carbohydrates gal alpha-1-3 gal present a similar lytic activity against T.cruzi at the same concentrations of purified anti-gal antibodies. The DL activity was tested with several other lectins but Concanavalin A (Con A) specific for alpha-D-mannose and alpha-D-glucose was the only one also presenting lytic activity. The lectins and anti-gal antibodies lytic activity can be inhibited by specific carbohydrates suggesting that this phenomenon is related to the capability of these lectins or anti-gal antibodies to bind to a crucial surface component of T. cruzi. Moreover, the infectivity of T. cruzi blood forms to mice was clearly inactivated by incubation with acute chagasic sera (ACS) but not by ACS absorbed by immunoaffinity chromatography with mouse laminin, a strong evidence that high levels of anti-gal antibodies participate in the decline of the parasitaemia from the acute to the chronic phase in Chagas disease.