A heparin-binding activity on Leishmania amastigotes which mediates adhesion to cellular proteoglycans.
A heparin-binding activity on Leishmania amastigotes which mediates adhesion to cellular proteoglycans.
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DOI：
10.1083/jcb.123.3.759
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发表时间：
1993-11
期刊：
影响因子：
--
通讯作者：
Mosser DM
中科院分区：
文献类型：
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作者：
Love DC;Esko JD;Mosser DM
利什曼原虫的细胞内无鞭毛体形式负责哺乳动物宿主中利什曼原虫感染的细胞间传播。在这份报告中，我们确定了高亲和力，肝素结合活性的表面上的无鞭毛体形式的利什曼原虫。亚马逊利什曼原虫的无鞭毛体每个细胞结合大约120，000个肝素分子，Kd为8.8 × 10（-8）M。这种肝素结合活性通过硫酸乙酰肝素蛋白聚糖介导无鞭毛体与哺乳动物细胞的粘附，硫酸乙酰肝素蛋白聚糖在哺乳动物细胞表面表达。无鞭毛体有效地结合到各种表达细胞表面蛋白聚糖的贴壁细胞。与野生型CHO细胞，结合无鞭毛体贪婪，CHO细胞与硫酸乙酰肝素蛋白聚糖生物合成的遗传缺陷或细胞肝素酶处理未能结合无鞭毛体，即使在高寄生虫输入剂量。表达正常水平的低硫酸化乙酰肝素的细胞几乎与野生型细胞一样有效地结合无鞭毛体。无鞭毛体与野生型非髓细胞的粘附几乎完全抑制了微摩尔量的可溶性肝素或硫酸乙酰肝素，但不是通过添加其他硫酸多糖。l无鞭毛体与巨噬细胞的结合，然而，只有60%的无鞭毛体与肝素预处理后，这表明巨噬细胞有一个额外的机制，识别无鞭毛体。这些结果表明，利什曼原虫无鞭毛体表达的高亲和力，肝素结合活性的表面上，可以与哺乳动物细胞上的硫酸乙酰肝素蛋白聚糖相互作用。这种相互作用可能是无鞭毛体入侵宿主细胞的重要第一步。
The intracellular amastigote form of leishmania is responsible for the cell-to-cell spread of leishmania infection in the mammalian host. In this report, we identify a high-affinity, heparin-binding activity on the surface of the amastigote form of leishmania. Amastigotes of Leishmania amazonensis bound approximately 120,000 molecules of heparin per cell, with a Kd of 8.8 x 10(-8) M. This heparin-binding activity mediates the adhesion of amastigotes to mammalian cells via heparan sulfate proteoglycans, which are expressed on the surface of mammalian cells. Amastigotes bound efficiently to a variety of adherent cells which express cell-surface proteoglycans. Unlike wild-type CHO cells, which bound amastigotes avidly, CHO cells with genetic deficiencies in heparan sulfate proteoglycan biosynthesis or cells treated with heparitinase failed to bind amastigotes even at high parasite-input dosages. Cells which express normal levels of undersulfated heparan bound amastigotes nearly as efficiently as did wild-type cells. The adhesion of amastigotes to wild-type nonmyeloid cells was almost completely inhibited by the addition of micromolar amounts of soluble heparin or heparan sulfate but not by the addition of other sulfated polysaccharides.l Binding of amastigotes to macrophages, however, was inhibited by only 60% after pretreatment of amastigotes with heparin, suggesting that macrophages have an additional mechanism for recognizing amastigotes. These results suggest that leishmania amastigotes express a high-affinity, heparin-binding activity on their surface which can interact with heparan sulfate proteoglycans on mammalian cells. This interaction may represent an important first step in the invasion of host cells by amastigotes.