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Vascular endothelial cells (ECs) link hemostasis, thrombosis, and complement. ECs synthesize both the clotting initiator von Willebrand factor (VWF) and the complement regulator factor H (FH). VWF is stored in EC Weibel-Palade bodies (WPBs), but the intracellular location of FH is not well defined. We found that FH colocalizes with VWF in WPBs of human(More)
Polyspecific antibodies represent a first line of defense against infection and regulate inflammation, properties hypothesized to rely on their ability to interact with multiple antigens. We demonstrated that IgG exposure to pro-oxidative ferrous ions or to reactive oxygen species enhances paratope flexibility and hydrophobicity, leading to expansion of the(More)
Replacement therapy in hemophilia A with exogenous coagulation factor VIII (FVIII) often results in the development of FVIII-neutralizing antibodies, referred to as inhibitors. Despite of large number of studies on the functional properties of FVIII inhibitors, detailed physicochemical characterization of their interactions is not available. Here we studied(More)
Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or(More)
Reactive oxygen species (ROS) released from activated phagocytes are involved in the innate immune defense against pathogens. However, when released in excess and when the antioxidant systems are impaired, ROS may induce cellular and tissue damage and dissociation of iron ions or iron containing compounds (heme) from protein-bound state. Free iron ions and(More)
Despite remarkable progress in the control of infectious diseases through vaccination, better delivery systems have been poorly explored. There is renewed interest in the discovery of novel vaccines and adjuvants owing to emerging and reemerging diseases and the burden and complexity of chronic infectious diseases. Conversely, the need for rapid local,(More)
Intravenous immunoglobulins (IVIg) exert a broad range of immunoregularoty functions that provide a basis for the beneficial effects of IVIg in autoimmune and systemic inflammatory disorders. This review focuses on the effects f IVIg on humoral and cellular inmmunity that may be of relevance for the treatment of inflammatory neurological diseases.
Kawasaki disease (KD) is an acute febrile childhood vasculitis, associated with the development of coronary artery abnormalities in 25-30% of untreated patients. The aetiopathogenesis is not well known but it is accepted that an undefined infectious trigger in genetically predisposed individuals results in the disease. KD is characterized by an endothelial(More)
Various pathological processes are accompanied by release of high amounts of free heme into the circulation. We demonstrated by kinetic, thermodynamic, and spectroscopic analyses that antibodies have an intrinsic ability to bind heme. This binding resulted in a decrease in the conformational freedom of the antibody paratopes and in a change in the nature of(More)
Administration of attenuated pathogenic T cell clones, a procedure known as T cell vaccination, induces CD8+ T cells specific for peptides derived from the Vbeta-chain of the TCR presented by the MHC class Ib molecule, Qa-1 expressed on the vaccine cells. These regulatory CD8+ T cells have the capacity to control the activation of endogenous T cells(More)