Event Title
Immune complex-induced, nitric oxide-mediated vascular endothelial cell death by phagocytes is prevented with decoy FcgReceptors
Location
Georgia
Start Date
12-5-2015 1:00 PM
Description
The interaction of Fc gamma receptors (FcγRs) expressed on inflammatory cells and immune-complexes (ICs) results in blood vessel damage during autoimmune vasculitis. Thus we tested if uncoupling these interactions of FcγRs and ICs prevented endothelium damage. Herein, we demonstrate that dimeric FcγR-Igs prevented apoptosis of antibody-coated human umbilical vein endothelial cells (HUVECs) mediated by nitric oxide (NO) released from murine macrophages. FcγR-Igs inhibited the IC-induced upregulation of inducible nitric oxide synthase and NO release by macrophages there by prevented the expression of pro-apoptotic genes in HUVECs. FcgR-Igs did not affect exogenous NO-induced upregulation of pro-apoptotic genes in HUVECs. The co-localization of FcγR-Igs and ICs in the vascular regions of various organs revealed that FcγRs-Igs bind to ICs and prevent vascular endothelial cell death in vivo. In conclusion, these data suggest that IC-induced NO is a major factor promoting blood vessel inflammation and endothelial cell death during IC-mediated vasculitis which can be effectively blocked by dimeric decoy FcγRs.
Immune complex-induced, nitric oxide-mediated vascular endothelial cell death by phagocytes is prevented with decoy FcgReceptors
Georgia
The interaction of Fc gamma receptors (FcγRs) expressed on inflammatory cells and immune-complexes (ICs) results in blood vessel damage during autoimmune vasculitis. Thus we tested if uncoupling these interactions of FcγRs and ICs prevented endothelium damage. Herein, we demonstrate that dimeric FcγR-Igs prevented apoptosis of antibody-coated human umbilical vein endothelial cells (HUVECs) mediated by nitric oxide (NO) released from murine macrophages. FcγR-Igs inhibited the IC-induced upregulation of inducible nitric oxide synthase and NO release by macrophages there by prevented the expression of pro-apoptotic genes in HUVECs. FcgR-Igs did not affect exogenous NO-induced upregulation of pro-apoptotic genes in HUVECs. The co-localization of FcγR-Igs and ICs in the vascular regions of various organs revealed that FcγRs-Igs bind to ICs and prevent vascular endothelial cell death in vivo. In conclusion, these data suggest that IC-induced NO is a major factor promoting blood vessel inflammation and endothelial cell death during IC-mediated vasculitis which can be effectively blocked by dimeric decoy FcγRs.