リピドＡの化学構造　　細菌リポ多糖の主要な免疫調節活性の中心

DOI Web Site 被引用文献4件 参考文献120件
  • Alexander Christian
    Research Center Borstel, Center of Medicine and Bio-Sciences Department of Immunochemistry and Biochemical Microbiology
  • Zähringer Ulrich
    Research Center Borstel, Center of Medicine and Bio-Sciences Department of Immunochemistry and Biochemical Microbiology
  • 小久保 晋
    大阪大学大学院理学研究科
  • 隅田 泰生
    大阪大学大学院理学研究科

書誌事項

タイトル別名
  • Chemical Structure of Lipid A. The Primary Immunomodulatory Center of Bacterial Lipopolysaccharides.
  • リピド A ノ カガク コウゾウ サイキン リポ タトウ ノ シュヨウ ナ メンエキ チョウセツ カッセイ ノ チュウシン ガン エイブン

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抄録

Lipopolysaccharides (LPS) are the major outer surface membrane components expressed by the vast majority of Gram-negative bacteria and have been identified to be extremely strong stimulators of innate or natural immunity in diverse eukaryotic species ranging from insects or plants to humans. Due to early observations on the induction of severe pathological forms of immunoactivation such as septic shock this class of bacterial surface molecules has been termed ‘endotoxins’. By combination of chemical analysis, mass spectrometry and NMR techniques, the chemical structures of LPS from a variety of Gram-negative bacteria have been characterized in detail. LPS consist of an extracellular poly- or oligosaccharide region that is anchored in the outer bacterial membrane by a specific glycolipid termed lipid A. The lipid A component has been identified to be the primary immunostimulatory center of LPS. An overview of major types of lipid A structures recently established is given, thus completing and updating previous reviews (1, 2). In the present review central structure-bioactivity-correlations are discussed with respect to immunoactivation of the mammalian phagocyte system. In addition to the classical group of strongly agonistic (highly endotoxic) forms of lipid A, several natural or synthetic lipid A structures have been identified that display comparatively low or even no phagocyte activation for a given mammalian species. Some members of the latter more heterogeneous group are capable to antagonize the effects of strongly stimulatory LPS/lipid A. LPS of Gram-negative bacteria have been found to express a certain degree of structural diversity with respect to three structural elements: the glycosyl part of lipid A (lipid A backbone), the number, charge and linkage of polar head-group substituents, and the number, position and chemical nature of various acyl residues directly or indirectly linked to the lipid A backbone. Among all these structural variations, the acylation pattern has been found to encode mostly for its strong agonistic or antagonistic immunostimulatory activities in various biosystems.

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