Structural prerequisites for endotoxic activity in the Limulus test as compared to cytokine production in mononuclear cells

T. Gutsmann, J. Howe, U. Z̈hringer, P. Garidel, A. B. Schromm, M. H.J. Koch, Y. Fujimoto, K. Fukase, I. Moriyon, G. Martínez-De-Tejada, K. Brandenburg

研究成果: Article査読

47 被引用数 (Scopus)

抄録

The structural prerequisites for lipopolysaccharide (LPS) and its partial structures for the activation of the Limulus clotting cascade (Limulus amebocyte lysate [LAL] test) are described and compared with the corresponding requirements for the activation of human immune cells such as mononuclear cells. A necessary, but not sufficient, structural motif for this is the presence of the 4ĝ2-phosphate-diglucosamine backbone recognition structure (ĝepitopeĝ) in lipid A. High activity is only expressed by assemblies of endotoxins, but this is largely independent of the type of supramolecular aggregate structure. A particular conformation of the epitope within the lipid A assembly must be present, which is influenced by addition of further saccharide units to the lipid A moiety, but also reacts slightly to the acylation pattern. In contrast, the cytokine production of human immune cells induced by LPS sensitively depends on the type of its aggregate structure. In the case of a hexa-acylated bisphosphorylated lipid A structure, high activity is only observed with cubic inverted aggregates. Furthermore, addition of antimicrobial agents (such as polymyxin B) leads to a nearly complete inhibition of cytokine production, whereas the reduction in the Limulus assay is much lower. These data are important since a reliable determination of endotoxin concentrations, in particular with respect to its ability to elicit severe infections, is of high interest.

本文言語English
ページ(範囲)39-47
ページ数9
ジャーナルInnate Immunity
16
1
DOI
出版ステータスPublished - 2010 2月
外部発表はい

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • 分子生物学
  • 細胞生物学
  • 感染症

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