The role of advanced oxidation protein products in regulation of dendritic cell function

• Published in: Free radical biology & medicine Vol. 32; no. 5; pp. 377 - 385
• Main Authors: Alderman, Charles J.J, Shah, Sachit, Foreman, John C, Chain, Benjamin M, Katz, David R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2002
• Subjects: Advanced oxidation protein products (AOPP); Animals; Antigens, CD - immunology; Antigens, CD - metabolism; Cattle; Cell Differentiation; Cell Division; Cells, Cultured; Danger hypothesis; Dendritic cell(s); Dendritic Cells - physiology; Dityrosine; Free radicals; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; HLA-DR Antigens - immunology; HLA-DR Antigens - metabolism; Humans; Hypochlorous Acid - metabolism; Immunomagnetic Separation; In Vitro Techniques; Interleukin-4 - metabolism; Lipopolysaccharides - metabolism; Monocytes - immunology; Monocytes - metabolism; Oxidation-Reduction; Oxidative mitogenesis; Oxidative stress; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reactive Oxygen Species - pharmacology; Serum Albumin, Bovine - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tyrosine - analogs & derivatives; Tyrosine - metabolism; Oxidative stress; Advanced oxidation protein products (AOPP); Reactive oxygen species; DMSO; MTT; TNF; LPS; BSA; Dendritic cell(s); FITC; Oxidative mitogenesis; GM-CSF; AGE; PBS; Free radicals; SDS; DTNB; IL-1; IL-4; PAGE; RAGE; TNBS; PBMC; Mab; AOPP; MDDC; APC; Danger hypothesis; FCS; HBSS; Dityrosine; DC
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(01)00735-3

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.