Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by Phagocytes Is Prevented with Decoy FcγReceptors.
Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcγRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcγRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcγR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcγR-Igs significantly inhibited the IC-induced upregulation of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release by murine monocytic cell line. However, FcγR-Igs did not affect the exogenously added NO-induced upregulation of pro-apoptotic genes such as Bax (15 fold), Bak (35 fold), cytochrome-C (11 fold) and caspase-3 (30 fold) in HUVECs. In conclusion, these data suggest that IC-induced NO could be one of the major inflammatory mediator promoting blood vessel inflammation and endothelial cell death during IC-mediated vasculitis which can be effectively blocked by dimeric decoy FcγRs.
Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
Ramanjaneya V R
RV
Mula
Department of Molecular Pathology Laboratory, Yerkes National Primate Research Centre, Atlanta, Georgia, United States of America.
Deepa
D
Machiah
Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
Lauren
L
Holland
Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
Xinyu
X
Wang
Department of Pharmacy Practice, Philadelphia College of Osteopathic Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
Harish
H
Parihar
Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
Avadhesh C
AC
Sharma
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America.
Periasamy
P
Selvaraj
Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
Rangaiah
R
Shashidharamurthy
D000936:Antigen-Antibody Complex / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*
D000936:Antigen-Antibody Complex; D018836:Inflammation Mediators; D017452:Receptors, IgG; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II