Event Title
Recombinant Dimeric FcgR-Ig Molecules
Location
Georgia Campus
Start Date
7-5-2014 1:00 PM
Description
Autoimmune vasculitis is an endothelial inflammatory disease that results from deposition of immune-complexes (ICs) in blood vessels. Interaction of FcγRs expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is prerequisite to prevent the blood vessel damage. Herein, we have shown that dimeric FcγR-Ig (CD16A-Ig and CD32A-Ig) molecules are able to block these interactions using in vitro and in vivo vasculitis models. FcγR-Igs could block 70% of RAW 267.4 cells binding to antibody-coated Human umbilical vein endothelial cells (HUVEC). FcγR-Igs significantly inhibited the IC-mediated expression of inducible nitric oxide synthase (iNOS) and Nitric oxide (NO) release in RAW 264.7 cells. We observed that exogenous NO induced the upregulation of pro-apoptotic genes such as Bax, Bak, caspase-3 and caspase-8 in HUVEC cells. Further, in vivo studies revealed that circulating ICs deposits in the capillaries of various vital organs but not in large arteries. Interestingly, dimeric FcγR-Igs are distributed in the areas where ICs are deposited. The co-localization of ICs and FcγR-Igs revealed that dimeric FcγR-Ig molecules bind specifically to ICs and thus prevent the vascular damage. Taken together, these results suggest that IC-induced NO might be a major factor promoting the blood vessel damage, which can effectively be blocked using recombinant dimeric FcγRs molecules during IC mediated vasculitis.
Recombinant Dimeric FcgR-Ig Molecules
Georgia Campus
Autoimmune vasculitis is an endothelial inflammatory disease that results from deposition of immune-complexes (ICs) in blood vessels. Interaction of FcγRs expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is prerequisite to prevent the blood vessel damage. Herein, we have shown that dimeric FcγR-Ig (CD16A-Ig and CD32A-Ig) molecules are able to block these interactions using in vitro and in vivo vasculitis models. FcγR-Igs could block 70% of RAW 267.4 cells binding to antibody-coated Human umbilical vein endothelial cells (HUVEC). FcγR-Igs significantly inhibited the IC-mediated expression of inducible nitric oxide synthase (iNOS) and Nitric oxide (NO) release in RAW 264.7 cells. We observed that exogenous NO induced the upregulation of pro-apoptotic genes such as Bax, Bak, caspase-3 and caspase-8 in HUVEC cells. Further, in vivo studies revealed that circulating ICs deposits in the capillaries of various vital organs but not in large arteries. Interestingly, dimeric FcγR-Igs are distributed in the areas where ICs are deposited. The co-localization of ICs and FcγR-Igs revealed that dimeric FcγR-Ig molecules bind specifically to ICs and thus prevent the vascular damage. Taken together, these results suggest that IC-induced NO might be a major factor promoting the blood vessel damage, which can effectively be blocked using recombinant dimeric FcγRs molecules during IC mediated vasculitis.