De Jesus Magdia, Park Chae Gyu, Su Ya, Goldman David L, Steinman Ralph M, Casadevall Arturo
Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
Med Mycol. 2008 Mar;46(2):153-62. doi: 10.1080/13693780701747182.
The fate of microbial polysaccharides in host tissues is an important consideration because these compounds are often immune modulators. Splenic marginal zone macrophages that express the C-type lectin receptor SIGN-R1, take up neutral polysaccharides such as dextran and the capsular polysaccharide of Streptococcus pneumoniae. Given that the major component of Cryptococcus neoformans capsular polysaccharide, glucuronoxylomannan (GXM), localizes in the spleen when injected intravenously, we investigated whether GXM uptake was mediated by splenic macrophages expressing the SIGN-R1 receptor in mice. No significant differences in the amount and location of GXM deposition were detected in the spleens of mice treated with a SIGN-R1 blocking antibody when compared to controls. Similarly, a blocking antibody to Dectin-1, a co-receptor of -SIGN-R1, had no effects on GXM distribution within the spleen. Histological examination of spleens from mice and rats injected with FITC-Dextran and GXM revealed no significant co-localization, with Dextran and GXM being found in marginal and red pulp macrophages, respectively. Hence we conclude that GXM was not deposited in marginal zone macrophages. However, GXM deposition was found in the red pulp. These results indicate that there is a selective localization of these polysaccharides to different receptors such as SIGN-R1 for FITC dextran in marginal zone and a to-be-identified receptor selectively expressed by red pulp macrophages for GXM.
微生物多糖在宿主组织中的命运是一个重要的考量因素,因为这些化合物通常是免疫调节剂。表达C型凝集素受体SIGN - R1的脾脏边缘区巨噬细胞会摄取中性多糖,如葡聚糖和肺炎链球菌的荚膜多糖。鉴于新型隐球菌荚膜多糖的主要成分葡糖醛酸木甘露聚糖(GXM)静脉注射后会定位于脾脏,我们研究了在小鼠中GXM的摄取是否由表达SIGN - R1受体的脾脏巨噬细胞介导。与对照组相比,在用SIGN - R1阻断抗体处理的小鼠脾脏中,未检测到GXM沉积量和位置的显著差异。同样,Dectin - 1(SIGN - R1的共受体)的阻断抗体对GXM在脾脏内的分布也没有影响。对注射了FITC - 葡聚糖和GXM的小鼠和大鼠的脾脏进行组织学检查发现,没有明显的共定位现象,葡聚糖和GXM分别存在于边缘区和红髓巨噬细胞中。因此我们得出结论,GXM没有沉积在边缘区巨噬细胞中。然而,在红髓中发现了GXM沉积。这些结果表明,这些多糖在不同受体上存在选择性定位,如边缘区中针对FITC葡聚糖的SIGN - R1,以及红髓巨噬细胞选择性表达的、有待确定的针对GXM的受体。