In vivo clearance of glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans:: A critical role for tissue macrophages

In vivo clearance of glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans:: A critical role for tissue macrophages
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DOI:
10.1086/322787
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发表时间:
2001-08-15
影响因子:
6.4
通讯作者:
Kozel, TR
Kozel, TR
中科院分区:
医学2区
文献类型:
--
作者:
Grinsell, M;Weinhold, LC;Kozel, TR

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新型隐球菌会导致艾滋病患者免疫功能低下,引发危及生命的脑膜炎。艾滋病隐球菌病的一个显着特征是主要荚膜多糖葡萄糖醛酸木甘露聚糖 (GXM) 的血清水平较高。可溶性 GXM 具有多种生物活性,可能有助于感染的发病机制。该研究的目的是进一步了解 GXM 的体内加工过程。给小鼠静脉注射GXM,并测定组织分布。使用脂质体封装的二氯亚甲基二膦酸盐的巨噬细胞自杀技术确定了巨噬细胞的作用。 GXM 从血清中清除,半衰期为 24-48 小时,但在富含单核吞噬细胞系统细胞的组织中无限期保留。巨噬细胞的消融降低了肝脏和脾脏中的 GXM,并增加了血清 GXM。结果确定了巨噬细胞在从血清中清除 GXM 中的关键作用,并将巨噬细胞确定为长期储存库。
Cryptococcus neoformans produces a life-threatening meningitis in patients who are immunocompromised by AIDS. A striking feature of cryptococcosis in AIDS is high serum levels of the major capsular polysaccharide, glucuronoxylomannan (GXM). Soluble GXM has numerous biologic activities that may contribute to the pathogenesis of infection. The objective of the study was to further understand in vivo processing of GXM. Mice were injected intravenously with GXM, and the tissue distribution was determined. A macrophage suicide technique that used liposome-encapsulated dichloromethylene diphosphonate determined the role of macrophages. GXM was cleared from serum with a half-life of 24-48 h but was retained for an indefinite period in tissues rich in cells of the mononuclear phagocyte system. Ablation of macrophages decreased GXM in the liver and spleen and increased serum GXM. The results identify a key role for macrophages in the clearance of GXM from serum and identify macrophages as a long-term reservoir for storage.