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

Immunology and Cell Biology - Tập 83 Số 4 - Trang 336-343 - 2005
Kosei Maemura1, Qizhi Zheng1, Tatehiko Wada1, Michitaka Ozaki1, Sonshin Takao1,2, Takashi Aikou3, Gregory B. Bulkley1, Andrew S. Klein4,1, Zhaoli Sun1
1Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
2Research Center for Life Science Resources, Kagoshima University Kagoshima Japan
3Department of Surgical Oncology and Digestive Surgery, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan
4Department of Surgery, Cedars Sinai Medical Center Los Angeles California USA

Tóm tắt

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.

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