THE TYPE-I MACROPHAGE SCAVENGER RECEPTOR BINDS TO GRAM-POSITIVE BACTERIA AND RECOGNIZES LIPOTEICHOIC ACID
THE TYPE-I MACROPHAGE SCAVENGER RECEPTOR BINDS TO GRAM-POSITIVE BACTERIA AND RECOGNIZES LIPOTEICHOIC ACID
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DOI：
10.1073/pnas.91.5.1863
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发表时间：
1994-03-01
影响因子：
11.1
通讯作者：
JOINER, KA
中科院分区：
文献类型：
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作者：
DUNNE, DW;RESNICK, D;JOINER, KA
巨噬细胞清道夫受体对多阴离子配体表现出异常广泛的结合特异性，并与动脉粥样硬化和各种宿主防御功能有关。在体外结合实验中，使用放射性标记的分泌型I型牛巨噬细胞清除受体，我们发现该受体与完整的革兰氏阳性细菌结合，包括化脓性链球菌、无乳链球菌、金黄色葡萄球菌、扁平肠球菌和单核增生李斯特菌。使用纯化的脂磷壁酸（一种阴离子聚合物，在大多数革兰氏阳性细菌表面表达）进行竞争结合研究表明，脂磷壁酸是清道夫受体配体，可能介导受体与革兰氏阳性细菌的结合。脂质胆酸与革兰氏阳性菌引起的脓毒性休克的发病机制有关，此前未发现宿主细胞受体。在革兰氏阳性败血症期间，清道夫受体可能通过清除组织和循环中的脂磷胆酸和/或完整细菌参与宿主防御。由于清道夫受体先前已被证明与革兰氏阴性细菌内毒素（脂多糖）结合并促进血流清除，这些受体可能为巨噬细胞识别和内化病原体及其细胞表面成分提供了一般机制。
Macrophage scavenger receptors exhibit unusually broad binding specificity for polyanionic ligands and have been implicated in atherosclerosis and various host defense functions. Using a radiolabeled, secreted form of the type I bovine macrophage scavenger receptor in an in vitro binding assay, we have found that this receptor binds to intact Gram-positive bacteria, including Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus, Enterococcus hirae, and Listeria monocytogenes. Competition binding studies using purified lipoteichoic acid, an anionic polymer expressed on the surface of most Gram-positive bacteria, show that lipoteichoic acids are scavenger receptor ligands and probably mediate binding of the receptor to Gram-positive bacteria. Lipoteichoic acids, for which no host cell receptors have previously been identified, are implicated in the pathogenesis of septic shock due to Gram-positive bacteria. Scavenger receptors may participate in host defense by clearing lipoteichoic acid and/or intact bacteria from tissues and the circulation during Gram-positive sepsis. Since scavenger receptors have been previously shown to bind to and facilitate bloodstream clearance of Gram-negative bacterial endotoxin (lipopolysaccharide), these receptors may provide a general mechanism for macrophage recognition and internalization of pathogens and their cell surface components.