Influence of lipoteichoic acid structure on recognition by the macrophage scavenger receptor
Influence of lipoteichoic acid structure on recognition by the macrophage scavenger receptor
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DOI：
10.1128/iai.64.8.3318-3325.1996
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发表时间：
1996-08-01
影响因子：
3.1
通讯作者：
Joiner, KA
中科院分区：
文献类型：
--
作者：
Greenberg, JW;Fischer, W;Joiner, KA
脂磷胆酸（LTAs）属于革兰氏阳性菌（GPB）的免疫刺激类分子。先前的研究表明，巨噬细胞清道夫受体（SR）是一种糖基化的三聚体跨膜蛋白，可能通过LTA直接与man - GPB结合。SR与其他配体的结合取决于配体重复负电荷的空间特征。因此，我们研究了不同电荷密度和分布的LTA物种的SR识别，通过确定这些LTA与代谢标记的SR与已知SR配体聚鸟苷酸包被的小球的结合能力，金黄色葡萄球菌LTA，经典的LTA类型（未支链的1,3-连接的聚甘油磷酸酯链共价结合到膜二酰基甘油糖脂上）。抑制SR结合的IC50浓度为0.84 μ g/ml。当金黄色葡萄球菌LTA通过去除聚甘油磷酸酯骨架上的酯连接丙氨酸而使其带更多负电荷时，IC50降至0.23 μ g/ml。粪肠球菌、粪肠球菌、扁平肠球菌、单核增生李斯特菌、威氏李斯特菌和血链球菌的多甘油三酯LTA的IC(50)s为0.5 ~ 2.1 μ g/ml，支持负电荷与SR结合的作用，因此，被带正电的糖残基取代的肺炎链球菌和无性梭菌LTA的两性离子LTA没有结合能力。单甘油三酯分支影响脂聚糖的结合，而琥珀酰酯不影响。上述数据与之前在整个生物体中的发现相一致，并支持表面相关LTA作为GPB与sr结合的主要配体的作用。LTA和整个GPB与巨噬细胞的结合是启动摄取和降解还是导致信号转导仍有待确定。
Lipoteichoic acids (LTAs) belong to the immunostimulatory class of molecules of gram-positive bacteria (GPB). Previous investigations showed that the macrophage scavenger receptor (SR), a glycosylated trimeric transmembrane protein, binds directly to manly GPB, possibly via LTA. SR binding to other ligands is dependent upon the spatial characteristics of the repeating negative charge of the ligand. We therefore investigated SR recognition of LTA species with various charge densities and distributions by determining the capacity of these LTAs to compete with the binding of metabolically labeled SR to beads coated with the known SR ligand polyguanylic acid, Staphylococcus aureus LTA, a classical LTA type (unbranched 1,3-linked polyglycerophosphate chain covalently bound to a membrane diacylglyceroglycolipid), had a 50% inhibitory concentration (IC50) for inhibition of SR binding of 0.84 mu g/ml. When the S. aureus LTA was rendered more negatively charged by removal of ester-linked alanine from the polyglycerophosphate backbone, the IC50 dropped to 0.23 mu g/ml. Other polyglycerophosphate LTAs from Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Listeria monocytogenes, Listeria welshimeri, and Streptococcus sanguis showed IC(50)s of 0.5 to 2.1 mu g/ml, supporting the role of negative charge in binding to SR, Accordingly, the zwitterionic LTA of Streptococcus pneumoniae and Clostridium innocuum LTA substituted with positively charged sugar residues had no binding capacity. Monoglycerophosphate branches, but not succinyl ester, affected binding of lipoglycans. The data presented above parallel the previous findings for whole organisms and support the role of surface-associated LTA as a major ligand of GPB for binding to SR. Whether binding of LTA and whole GPB to macrophages initiates uptake and degradation or results in signal transduction remains to be determined.