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巨噬细胞膜筏在克氏锥虫入侵过程中的作用

Participation of macrophage membrane rafts in Trypanosoma cruzi invasion process.

作者信息

Barrias E S, Dutra J M F, De Souza W, Carvalho T M U

机构信息

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, CCS, UFRJ, Ilha do Fundão, 21941-902 Rio de Janeiro, RJ, Brazil.

出版信息

Biochem Biophys Res Commun. 2007 Nov 23;363(3):828-34. doi: 10.1016/j.bbrc.2007.09.068. Epub 2007 Sep 25.

Abstract

Membrane rafts are small and dynamic regions enriched in sphingolipids, cholesterol, ganglioside GM1 and protein markers like flotillins, forming the flatter domains or caveolins, which are characterized as stable flask-shape invaginations. We explored whether membrane rafts participate in the entry of Trypanosoma cruzi's trypomastigotes into murine macrophages through transient depletion of macrophage membrane cholesterol with methyl-beta-cyclodextrin and treatment with filipin. These treatments led to a decrease in the trypomastigote invasion process. Macrophage pre incubated with increasing concentrations of cholera toxin B, that binds GM1, inhibited the adhesion and invasion of trypomastigote and amastigote forms. Immunofluorescence analysis demonstrated a colocalization of GM1, flotillin 1 and caveolin 1 in the T. cruzi parasitophorous vacuole. Taken together these data suggest that membrane rafts, including caveolae, are involved in the process of T. cruzi invasion of macrophages.

摘要

膜筏是富含鞘脂、胆固醇、神经节苷脂GM1和诸如浮舰蛋白等蛋白质标记物的小的动态区域,形成较扁平的结构域或小窝,其特征为稳定的烧瓶状内陷。我们通过用甲基-β-环糊精瞬时耗尽巨噬细胞膜胆固醇并用制霉菌素处理,探究了膜筏是否参与克氏锥虫锥鞭毛体进入小鼠巨噬细胞的过程。这些处理导致锥鞭毛体侵袭过程减少。用浓度递增的霍乱毒素B预孵育巨噬细胞(霍乱毒素B与GM1结合),抑制了锥鞭毛体和无鞭毛体形式的黏附和侵袭。免疫荧光分析表明GM1、浮舰蛋白1和小窝蛋白1在克氏锥虫寄生泡中共定位。这些数据综合起来表明,包括小窝在内的膜筏参与了克氏锥虫侵袭巨噬细胞的过程。

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