PMID- 27101012
OWN - NLM
STAT- MEDLINE
DCOM- 20170217
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 4
DP  - 2016
TI  - Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death by 
      Phagocytes Is Prevented with Decoy FcgammaReceptors.
PG  - e0153620
LID - 10.1371/journal.pone.0153620 [doi]
LID - e0153620
AB  - Autoimmune vasculitis is an endothelial inflammatory disease that results from 
      the deposition of immune-complexes (ICs) in blood vessels. The interaction 
      between Fcgamma receptors (FcgammaRs) 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 FcgammaRs and ICs prevents 
      endothelium damage. Herein, we demonstrate that dimeric FcgammaR-Igs prevented nitric 
      oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) 
      in an in vitro vasculitis model. Dimeric FcgammaR-Igs significantly inhibited the 
      IC-induced upregulation of inducible nitric oxide synthase (iNOS) and nitric 
      oxide (NO) release by murine monocytic cell line. However, FcgammaR-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 FcgammaRs.
FAU - Mula, Ramanjaneya V R
AU  - Mula RV
AD  - Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic 
      Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
FAU - Machiah, Deepa
AU  - Machiah D
AD  - Department of Molecular Pathology Laboratory, Yerkes National Primate Research 
      Centre, Atlanta, Georgia, United States of America.
FAU - Holland, Lauren
AU  - Holland L
AD  - Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic 
      Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
FAU - Wang, Xinyu
AU  - Wang X
AD  - Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic 
      Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
FAU - Parihar, Harish
AU  - Parihar H
AD  - Department of Pharmacy Practice, Philadelphia College of Osteopathic Medicine - 
      School of Pharmacy, Suwanee, Georgia, United States of America.
FAU - Sharma, Avadhesh C
AU  - Sharma AC
AD  - Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic 
      Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
FAU - Selvaraj, Periasamy
AU  - Selvaraj P
AD  - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, 
      Georgia, United States of America.
FAU - Shashidharamurthy, Rangaiah
AU  - Shashidharamurthy R
AD  - Department of Pharmaceutical Sciences, Philadelphia College of Osteopathic 
      Medicine - School of Pharmacy, Suwanee, Georgia, United States of America.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160421
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, IgG)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Antigen-Antibody Complex/*immunology
MH  - Apoptosis/*drug effects
MH  - Endothelium, Vascular/*cytology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Nitric Oxide/*pharmacology
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Phagocytes/*immunology
MH  - Receptors, IgG/*immunology
PMC - PMC4839578
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/04/23 06:00
MHDA- 2017/02/18 06:00
PMCR- 2016/04/21
CRDT- 2016/04/22 06:00
PHST- 2016/02/18 00:00 [received]
PHST- 2016/03/31 00:00 [accepted]
PHST- 2016/04/22 06:00 [entrez]
PHST- 2016/04/23 06:00 [pubmed]
PHST- 2017/02/18 06:00 [medline]
PHST- 2016/04/21 00:00 [pmc-release]
AID - PONE-D-16-07091 [pii]
AID - 10.1371/journal.pone.0153620 [doi]
PST - epublish
SO  - PLoS One. 2016 Apr 21;11(4):e0153620. doi: 10.1371/journal.pone.0153620. 
      eCollection 2016.