Enhancement of neutrophil autophagy by an IVIG preparation against multidrug-resistant bacteria as well as drug-sensitive strains

  • Hiroshi Itoh
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Hidemasa Matsuo
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Naoko Kitamura
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Sho Yamamoto
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Takeshi Higuchi
    Department of Clinical Laboratory, Kyoto University Hospital , Kyoto , Japan
  • Hiromu Takematsu
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Yasuhiko Kamikubo
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Tadakazu Kondo
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Kouhei Yamashita
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Masataka Sasada
    Department of Hematology and Oncology, Shiga Medical Center for Adults , Shiga , Japan
  • Akifumi Takaori-Kondo
    Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University , Kyoto , Japan
  • Souichi Adachi
    Department of Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto , Japan

書誌事項

公開日
2015-04-23
資源種別
journal article
権利情報
  • https://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1189/jlb.4a0813-422rrr
公開者
Oxford University Press (OUP)

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<jats:title>Abstract</jats:title> <jats:p>Autophagy occurs in human neutrophils after the phagocytosis of multidrug-resistant bacteria and drug-sensitive strains, including Escherichia coli and Pseudomonas aeruginosa. The present study detected autophagy by immunoblot analysis of LC3B conversion, by confocal scanning microscopic examination of LC3B aggregate formation and by transmission electron microscopic examination of bacteria-containing autophagosomes. Patients with severe bacterial infections are often treated with IVIG alongside antimicrobial agents. Here, we showed that IVIG induced neutrophil-mediated phagocytosis of multidrug-resistant strains. Compared with untreated neutrophils, neutrophils exposed to IVIG showed increased levels of bacterial cell killing, phagocytosis, O2− release, MPO release, and NET formation. IVIG also increased autophagy in these cells. Inhibiting the late phase of autophagy (fusion of lysosomes with autophagosomes) with bafilomycin A1-reduced, neutrophil-mediated bactericidal activity. These findings indicate that autophagy plays a critical role in the bactericidal activity mediated by human neutrophils. Furthermore, the autophagosomes within the neutrophils contained bacteria only and their organelles only, or both bacteria and their organelles, a previously undocumented observation. Taken together, these results suggest that the contents of neutrophil autophagosomes may be derived from specific autophagic systems, which provide the neutrophil with an advantage. Thus, IVIG promotes the neutrophil-mediated killing of multidrug-resistant bacteria as well as drug-sensitive strains.</jats:p>

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