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鉴定宿主巨噬细胞表面的巨唾液酸糖蛋白(CD68)为美洲利什曼原虫细胞间黏附分子(ICAM-L)的受体。

Identification of macrosialin (CD68) on the surface of host macrophages as the receptor for the intercellular adhesive molecule (ICAM-L) of Leishmania amazonensis.

机构信息

Division of Infectious Disease and Immunology, Academia Sinica, (IMBS) No. 128, Academia Road Sec. 2, Nan-Kang, Taipei 11529, Taiwan, ROC.

出版信息

Int J Parasitol. 2009 Dec;39(14):1539-50. doi: 10.1016/j.ijpara.2009.06.001. Epub 2009 Jun 18.

Abstract

The intercellular adhesive molecule, ICAM-L, of Leishmania amazonensis is known to block the attachment as well as internalisation of Leishmania for infection in host macrophages. We employed monoclonal antibodies (mAb) to the surface molecules of a macrophage to block the attachment of ICAM-L to the macrophage surface and identified that CD68 macrosialin is likely the receptor molecule on the macrophage for ICAM-L. We then demonstrated physical interaction between ICAM-L and macrosialin by co-immunoprecipitation of macrosialin with ICAM-L or vice versa. Finally, macrosialin is expressed in macrosialin-negative murine fibroblast cell line NCTC clone 2555 and demonstrates that both ICAM-L and promastigotes of L. amazonensis can bind to the CD68 transfectant. We thus conclude that CD68 macrosialin is the receptor on host macrophages for ICAM-L. Also, involvement of ICAM-L-macrosialin interaction in other Leishmania species and other mammalian macrophages were demonstrated, indicating the biological relevance of this ligand-receptor interaction.

摘要

已知美洲利什曼原虫的细胞间黏附分子 ICAM-L 可阻止利什曼原虫附着并内化感染宿主巨噬细胞。我们利用针对巨噬细胞表面分子的单克隆抗体(mAb)阻断 ICAM-L 与巨噬细胞表面的附着,并鉴定出巨噬细胞上的 CD68 macrosialin 可能是 ICAM-L 的受体分子。然后,我们通过共免疫沉淀证明了 ICAM-L 和 macrosialin 之间的物理相互作用,或者反之亦然。最后,macrosialin 在 macrosialin 阴性的鼠成纤维细胞系 NCTC clone 2555 中表达,并表明 ICAM-L 和 L. amazonensis 的前鞭毛体都可以与 CD68 转染子结合。因此,我们得出结论,CD68 macrosialin 是宿主巨噬细胞上 ICAM-L 的受体。此外,还证明了 ICAM-L-macrosialin 相互作用在其他利什曼原虫物种和其他哺乳动物巨噬细胞中的参与,表明这种配体-受体相互作用具有生物学相关性。

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