The role of advanced oxidation protein products in regulation of dendritic cell function.
The basis for this study was the "injury hypothesis," which holds that release of micro-environmental constituents, such as reactive oxygen species and oxidants, acts as a signal, and potential activator, of dendritic cell (DC)-mediated antigen presentation. Following this oxidative stress, dityrosine containing cross-linked proteins, advanced oxidation protein products (AOPP), are known to be generated, and we proposed that they may serve as moieties that mediate such signals. Therefore, the effect of AOPP on DCs has been examined in vitro. There were no AOPP-induced changes in DC phenotype as judged by expression of typical surface costimulatory molecules. However, at higher cell concentrations AOPP-treated DCs were more potent inducers in an oxidative mitogenesis assay than controls. Thus, AOPP may act like superantigens, allowing for bypass of upregulation of costimulation, and, either alone or in synergy with oxidants themselves, serving as amplifiers of DC function.
Alderman
Charles J J
CJ
Immunology Department, Windeyer Institute, University College London, London, England, UK.
Shah
Sachit
S
Foreman
John C
JC
Chain
Benjamin M
BM
Katz
David R
DR
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D018189:Immunomagnetic Separation; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D015703:Antigens, CD; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D015847:Interleukin-4; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D006997:Hypochlorous Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C007543:dityrosine