PMID- 29138419
OWN - NLM
STAT- MEDLINE
DCOM- 20190709
LR  - 20191008
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Nov 14
TI  - IVIG activates FcgammaRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress 
      inflammation after ICH in mice.
PG  - 15583
LID - 10.1038/s41598-017-15455-w [doi]
LID - 15583
AB  - Following intracerebral hemorrhage (ICH), the activation of mast cell contributes 
      to brain inflammation and brain injury. The mast cell activation is negatively 
      regulated by an inhibitory IgG-receptor. It's signals are mediated by SHIP (Src 
      homology 2-containing inositol 5' phosphatase), in particular SHIP1, which 
      activation leads to hydrolyzation of PIP3 (Phosphatidylinositol 
      (3,4,5)-trisphosphate (PtdIns(3,4,5)P(3), leading to the inhibition of calcium 
      mobilization and to the attenuation of mast cell activation. Intravenous 
      immunoglobulin (IVIG) is a FDA-approved drug containing IgG. We hypothesized that 
      IVIG will attenuate the ICH-induced mast cell activation via FcgammaRIIB/SHIP1 
      pathway, resulting in a decrease of brain inflammation, protection of the 
      blood-brain-barrier, and improvement of neurological functions after ICH. To 
      prove this hypothesis we employed the ICH collagenase mouse model. We 
      demonstrated that while ICH induced mast cell activation/degranulation, IVIG 
      attenuated post-ICH mast cell activation. Mast cell deactivation resulted in 
      reduced inflammation, consequently attenuating brain edema and improving of 
      neurological functions after ICH. Furthermore using siRNA-induced in vivo 
      knockdown approach we demonstrated that beneficial effects of IVIG were mediated, 
      at least partly, via SHIP1/PIP3 pathway. We conclude that IVIG treatment 
      represents a promising therapeutic approach potentially able to decrease 
      mortality and morbidity after ICH in experimental models.
FAU - Akyol, Gokce Yilmaz
AU  - Akyol GY
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
FAU - Manaenko, Anatol
AU  - Manaenko A
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
AD  - Departments of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
FAU - Akyol, Onat
AU  - Akyol O
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
FAU - Solaroglu, Ihsan
AU  - Solaroglu I
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
FAU - Ho, Wing Mann
AU  - Ho WM
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
FAU - Ding, Yan
AU  - Ding Y
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
FAU - Flores, Jerry
AU  - Flores J
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
FAU - Zhang, John H
AU  - Zhang JH
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA.
AD  - Department of Anesthesiology, Loma Linda University, Loma Linda, CA, USA.
FAU - Tang, Jiping
AU  - Tang J
AD  - Departments of Basic Science, Loma Linda University, Loma Linda, CA, USA. 
      jtang@llu.edu.
LA  - eng
GR  - P01 NS082184/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20171114
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Fcgr2b protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, IgG)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - EC 3.1.3.86 (Inpp5d protein, mouse)
RN  - EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases)
RN  - EC 3.4.24.- (Collagenases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Administration, Intravenous
MH  - Animals
MH  - Blood-Brain Barrier/drug effects
MH  - Brain/drug effects/metabolism/physiopathology
MH  - Calcium/metabolism
MH  - Cerebral Hemorrhage/*drug therapy/genetics/immunology/pathology
MH  - Collagenases/*genetics/immunology
MH  - Disease Models, Animal
MH  - Humans
MH  - Immunoglobulin G/administration & dosage
MH  - Inflammation/*drug therapy/genetics/immunology/pathology
MH  - Mast Cells/drug effects/metabolism
MH  - Mice
MH  - Phosphatidylinositol Phosphates/metabolism
MH  - Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/*genetics
MH  - RNA, Small Interfering/genetics
MH  - Receptors, IgG/*genetics/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC5686215
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/16 06:00
MHDA- 2019/07/10 06:00
PMCR- 2017/11/14
CRDT- 2017/11/16 06:00
PHST- 2017/04/19 00:00 [received]
PHST- 2017/10/19 00:00 [accepted]
PHST- 2017/11/16 06:00 [entrez]
PHST- 2017/11/16 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2017/11/14 00:00 [pmc-release]
AID - 10.1038/s41598-017-15455-w [pii]
AID - 15455 [pii]
AID - 10.1038/s41598-017-15455-w [doi]
PST - epublish
SO  - Sci Rep. 2017 Nov 14;7(1):15583. doi: 10.1038/s41598-017-15455-w.