Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells

Kosei Maemura, Qizhi Zheng, Tatehiko Wada, Michitaka Ozaki, Sonshin Takao, Takashi Aikou, Gregory B. Bulkley, Andrew S. Klein, Zhaoli Sun

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Kupffer cells (KC) act as APC in the liver and play a major role in the clearance of gut-derived antigens and pathogens entering the liver with portal venous blood. Antigen presentation by KC has been implicated in regulation of the local and systemic immune responses. In this study, modulation of KC antigen presentation by antioxidants and the role of reactive oxygen species (ROS) as essential mediators of antigen presentation in KC were investigated. Co-culture of KC with ovalbumin (OVA) antigens resulted in upstream intracellular endogenous ROS generation and increased expression of MHC class II and costimulator molecules, and consequent OVA-specific CD4+ T-cell proliferation in response to antigen presentation by KC. Scavenging of KC ROS by antioxidants, or blocking of KC ROS generation by specific inhibitors of NADPH oxidase and/or xanthine oxidase, or by specific inhibitors of the mitochondrial electron transport chain, significantly decreased OVA-specific T-cell proliferation in response to antigen presentation by KC. Increased expression of MHC class II and costimulatory molecules in KC pulsed with OVA antigens was blocked by inhibiting ROS generation enzymatically. Intracellular endogenous ROS generation during antigen processing may therefore provide essential secondary signalling for KC antigen presentation.

Original languageEnglish (US)
Pages (from-to)336-343
Number of pages8
JournalImmunology and Cell Biology
Volume83
Issue number4
DOIs
StatePublished - Aug 2005

Keywords

  • Antigen presentation
  • Kupffer cell
  • Liver
  • Reactive oxygen species (ROS)
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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