Mucin AgC10 from Trypanosoma cruzi Interferes with L-selectin-mediated monocyte adhesion.
Mucin AgC10 from Trypanosoma cruzi Interferes with L-selectin-mediated monocyte adhesion.
复制标题
来自克氏锥虫的粘蛋白 AgC10 干扰 L-选择素介导的单核细胞粘附。
DOI：
10.1128/iai.00794-09
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发表时间：
2010
影响因子：
3.1
通讯作者：
Fresno,Manuel
中科院分区：
文献类型：
--
作者：
Alcaide,Pilar;Lim,YawChin;Luscinskas,FrancisW;Fresno,Manuel
原生动物寄生虫克鲁兹锥虫进化出复杂的系统来逃避免疫反应。有效的免疫反应的一个重要要求是从血液中招募适当的免疫细胞到感染部位。在这里，我们展示了一种粘蛋白的表达和分泌，由亚环感染形式。CRUZI，AgC10，能够干扰L-选择素介导的单核细胞黏附。因此，稳定表达L-选择素的U937单核细胞(U937LAM)与AgC10孵育后，其在流动状态下对P-选择素的黏附显著减少，这种黏附依赖于L-选择素。该处理还可显著抑制U937LAM的AgC10和人原代单核细胞与激活的血管内皮细胞的黏附。这种作用是L-选择素所特有的，因为血管细胞黏附分子-1介导的黏附不受AgC10的影响。AgC10的这种作用可能是由于它能够诱导L-选择素从单核细胞膜上脱落，因为药物阻断这种脱落阻止了AgC10的活性。这是首次描述了一种防止寄生虫将白细胞黏附到内皮细胞的机制，并代表了一种新的潜在对策，以避免产生正确的免疫反应。
The protozoan parasiteTrypanosoma cruzihas evolved sophisticated systems to evade the immune response. An important requirement for a productive immune response is recruitment of the appropriate immune cells from the bloodstream to the sites of infection. Here, we show that a mucin expressed and secreted by the metacyclic infective form ofT. cruzi, AgC10, is able to interfere with L-selectin-mediated monocyte adhesion. Thus, incubation of U937 monocytic cells stably expressing L-selectin (U937LAM) with AgC10 strongly reduced their adhesion on P-selectin under flow, which is dependent on L-selectin. This treatment also results in a significant inhibition by AgC10 of U937LAM and human primary monocyte adhesion to activated vascular endothelium. This effect was specific for L-selectin, because vascular cell adhesion molecule 1 (VCAM-1)-mediated adhesion was not affected by AgC10 pretreatment. This effect of AgC10 is likely due to its ability to induce L-selectin shedding from the monocyte membrane, since pharmacologic blocking of this shedding prevents AgC10 activity. This is the first description of a mechanism that prevents leukocyte adhesion to the endothelium by a parasite and represents a new potential countermeasure to evade the generation of a correct immune response.