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Author Notes:
E-mail: rangaiahsh@pcom.edu
Conceived and designed the experiments: RS.
Performed the experiments: RVM DM LH.
Analyzed the data: HP XW ACS PS.
Contributed reagents/materials/analysis tools: XW ACS PS.
Wrote the paper: RS.
The authors thank Drs. Kenneth Slavik (CSO), Jennifer Gooch and Ms. Anjavi Sharma for critical reading of the manuscript.
The authors have declared that no competing interests exist.
Subjects:
Research Funding:
This work was supported by American Heart Association Award (11SDG5710004) and Chief Scientific Officer (CSO) funding from Philadelphia College of Osteopathic Medicine to RS and XW.
Keywords:
- Science & Technology
- EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
- INFLAMMATORY-BOWEL-DISEASE
- NEUTROPHIL RECRUITMENT
- TISSUE-INJURY
- L-ARGININE
- SYNTHASE
- EXPRESSION
- ACTIVATION
- ARTHRITIS
- Nitric oxide
- Inflammation
- Apoptosis
- Endothelial cells
- Inflammatory diseases
- Vasculitis
- Cell death
- Cytokines
Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by Phagocytes Is Prevented with Decoy Fc gamma Receptors
Abstract:
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 FcγRIgs 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.
Copyright information:
© 2016 Mula et al
This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
