論文

査読有り 国際誌
2018年6月23日

Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides.

Scandinavian journal of immunology
  • Naoto Yoshino
  • ,
  • Ryosuke Takeshita
  • ,
  • Hanae Kawamura
  • ,
  • Kazuyuki Murakami
  • ,
  • Yutaka Sasaki
  • ,
  • Ikumi Sugiyama
  • ,
  • Yasuyuki Sadzuka
  • ,
  • Masahiro Kagabu
  • ,
  • Toru Sugiyama
  • ,
  • Yasushi Muraki
  • ,
  • Shigehiro Sato

開始ページ
e12698
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/sji.12698

Cyclic lipopeptides such as surfactin and polymyxin have potent mucosal adjuvant properties. Cyclic lipopeptides are tensioactive compounds but the relationship between adjuvanticity and surface activity is unknown. Here, we show that the critical micelle concentration (cmc) of surfactant and particle size of the surfactant-protein complex are important determinants of cyclic lipopeptide adjuvanticity. We found that the diameter of cyclic lipopeptide-ovalbumin (OVA) complex particles was significantly larger than that in the solutions of OVA alone at cyclic lipopeptide concentrations above the cmc. OVA-specific antibody titers in mice immunized intranasally with OVA and a cyclic lipopeptide at concentrations above its cmc were significantly higher than those in mice immunized with OVA plus the same dose of the cyclic lipopeptide but administered with formulations in which cyclic lipopeptide concentration was below the cmc. Thus, the concentration of the cyclic lipopeptide in the formulation at immunization, but not its overall dose, was critical for its adjuvanticity. Furthermore, two types of aggregates, the cyclic lipopeptide simplex micelles and the cyclic lipopeptide-OVA complex micelles, were found in formulations with SF concentrations above its cmc. Degranulation of mast cells exposed to SF simplex micelles was more pronounced when SF concentration was above the cmc. In conclusion, our study showed that surface activity properties, such as the cmc and the size of surfactant-protein complex contribute to the adjuvanticity of cyclic lipopeptides. Our study proposes a novel idea that cmc is a key parameter for tensioactive adjuvants. This article is protected by copyright. All rights reserved.

リンク情報
DOI
https://doi.org/10.1111/sji.12698
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29935085

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