title: Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells.
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.
authors: Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Kosei
authors: K
authors: Maemura
authors: Qizhi
authors: Q
authors: Zheng
authors: Tatehiko
authors: T
authors: Wada
authors: Michitaka
authors: M
authors: Ozaki
authors: Sonshin
authors: S
authors: Takao
authors: Takashi
authors: T
authors: Aikou
authors: Gregory B
authors: GB
authors: Bulkley
authors: Andrew S
authors: AS
authors: Klein
authors: Zhaoli
authors: Z
authors: Sun
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000975:Antioxidants / Q000494:pharmacology; D018122:B7-1 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000032:analysis / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018122:B7-1 Antigen; D019013:CD40 Antigens; D004791:Enzyme Inhibitors; D000949:Histocompatibility Antigens Class II; D017382:Reactive Oxygen Species; D012402:Rotenone; D010047:Ovalbumin; D006861:Hydrogen Peroxide