Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by Phagocytes Is Prevented with Decoy FcγReceptors

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153620-e0153620
• Main Authors: Mula, Ramanjaneya V R, Machiah, Deepa, Holland, Lauren, Wang, Xinyu, Parihar, Harish, Sharma, Avadhesh C, Selvaraj, Periasamy, Shashidharamurthy, Rangaiah
• Format: Article
• Language: English
• Subjects: Antigen-Antibody Complex - immunology; Apoptosis; Apoptosis - drug effects; Biology and Life Sciences; Blood; Blood vessels; Caspase; Caspase-3; Cell adhesion & migration; Cell death; Cytochrome; Cytochrome c; Damage prevention; Endothelial cells; Endothelium; Endothelium, Vascular - cytology; Human Umbilical Vein Endothelial Cells; Humans; Inflammation Mediators - metabolism; Kinases; Medicine and Health Sciences; Monocytes; Nitric oxide; Nitric Oxide - pharmacology; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Osteopathic medicine; Phagocytes; Phagocytes - immunology; Receptors; Receptors, IgG - immunology; Rodents; Umbilical vein; Vasculitis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153620

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.