alexa Oxidized beta2-glycoprotein I induces human dendritic cell maturation and promotes a T helper type 1 response.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Buttari B, Profumo E, Mattei V, Siracusano A, Ortona E,

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Abstract The human plasma protein beta2-glycoprotein I (beta2-GPI) is the most common target for antiphospholipid antibodies associated with thrombotic events in chronic disorders related to endothelial cell dysfunction. Crucial information is needed to clarify why this self-abundant protein is targeted by autoimmune responses. In this study, we investigated whether oxidative modification of beta2-GPI, either spontaneous in culture wells or induced by treatment with H2O2, renders this self-protein able to activate immature monocyte-derived dendritic cells (DCs) from healthy human donors. Oxidized beta2-GPI caused DCs to mature so that CD83 appeared and CD80, CD86, human leukocyte antigen-D region related (HLA-DR), and CD40 increased. The interaction between oxidized beta2-GPI and DCs specifically stimulated these cells to secrete interleukin 12 (IL-12), IL-1beta, IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and IL-10. Oxidized beta2-GPI-stimulated DCs had increased allostimulatory ability and primed naive T lymphocytes, thus inducing T helper 1 (Th1) polarization. The interaction between oxidized beta2-GPI and DCs involved interleukin-1 receptor associated kinase (IRAK) phosphorylation and nuclear factor kappaB (NFkappaB) activation. Pretreatment of beta2-GPI with the antioxidant alpha-tocopherol prevented DC maturation. These findings show that human oxidized beta2-GPI, probably by interacting with a member of the Toll-like receptor (TLR) family, causes DCs to mature. Because this key beta2-GPI function requires oxidative modification, in several chronic disorders related to endothelial cell dysfunction oxidative stress might trigger the "autoimmune spiral." This article was published in Blood and referenced in Journal of Cytology & Histology

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