A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems

DOI Web Site 被引用文献12件
  • Ryosuke Takii
    Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan
  • Tomoko Kadowaki
    Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan
  • Atsuyo Baba
    Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan
  • Takayuki Tsukuba
    Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan
  • Kenji Yamamoto
    Department of Pharmacology, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan

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<jats:title>ABSTRACT</jats:title><jats:p>Arg-gingipain (Rgp) and Lys-gingipain (Kgp) are<jats:italic>Porphyromonas gingivalis</jats:italic>cysteine proteinases implicated as major virulence factors in pathologies of periodontitis. We purified a 660-kDa cell-associated gingipain complex existing as a homodimer of two catalytically active monomers which comprises their catalytic and adhesin domains. Electron microscopy revealed that the complex was composed of a globular particle with a 10-nm external diameter possessing one or two electron-dense hole-like structures. Two-dimensional gel electrophoresis and immunoblot analyses revealed the association of lipopolysaccharide (LPS) with the catalytic domains and a hemagglutinin domain, Hgp44, of Rgp and Kgp in the complex. The complex significantly degraded human type I collagen and elastin and strongly disrupted viability of human gingival fibroblasts and umbilical vein endotherial cells with an efficiency which was higher than that of the monomeric gingipains. The native complex produced only a small amount of nitrogen dioxide, tumor necrosis factor alpha, and interleukin-6 by macrophages, whereas the heat-denatured complex resulted in increased production. Inhibition of the proteolytic activities of the gingipain complex did not up-regulate the cytokine production, indicating that the functional domains in LPS are structurally masked by the complex proteins. These results indicate the importance of the complex in evasion of host defense mechanisms as well as in host tissue breakdown.</jats:p>

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