PMID- 20029397
OWN - NLM
STAT- MEDLINE
DCOM- 20100730
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 5
DP  - 2010 May
TI  - Adoptive transfer of ex vivo HO-1 modified bone marrow-derived macrophages 
      prevents liver ischemia and reperfusion injury.
PG  - 1019-25
LID - 10.1038/mt.2009.285 [doi]
AB  - Macrophages play a critical role in the pathophysiology of liver ischemia and 
      reperfusion (IR) injury (IRI). However, macrophages that overexpress antioxidant 
      heme oxygenase-1 (HO-1) may exert profound anti-inflammatory functions. This 
      study explores the cytoprotective effects and mechanisms of ex vivo modified 
      HO-1-expressing bone marrow-derived macrophages (BMDMs) in well-defined mouse 
      model of liver warm ischemia followed by reperfusion. Adoptive transfer of 
      Ad-HO-1-transduced macrophages prevented IR-induced hepatocellular damage, as 
      evidenced by depressed serum glutamic-oxaloacetic transaminase (sGOT) levels and 
      preserved liver histology (Suzuki scores), compared to Ad-beta-gal controls. This 
      beneficial effect was reversed following concomitant treatment with HO-1 siRNA. 
      Ad-HO-1-transfected macrophages significantly decreased local neutrophil 
      accumulation, TNF-alpha/IL-1beta, IFN-gamma/E-selectin, and IP-10/MCP-1 
      expression, caspase-3 activity, and the frequency of apoptotic cells, as compared 
      with controls. Unlike in controls, Ad-HO-1-transfected macrophages markedly 
      increased hepatic expression of antiapoptotic Bcl-2/Bcl-xl and depressed 
      caspase-3 activity. These results establish the precedent for a novel 
      investigative tool and provide the rationale for a clinically attractive new 
      strategy in which native macrophages can be transfected ex vivo with 
      cytoprotective HO-1 and then infused, if needed, to prospective recipients 
      exposed to hepatic IR-mediated local inflammation, such as during liver 
      transplantation, resection, or trauma.
FAU - Ke, Bibo
AU  - Ke B
AD  - Department of Surgery, David Geffen School of Medicine at UCLA, Dumont-UCLA 
      Transplant Center, Los Angeles, California, USA.
FAU - Shen, Xiu-Da
AU  - Shen XD
FAU - Gao, Feng
AU  - Gao F
FAU - Ji, Haofeng
AU  - Ji H
FAU - Qiao, Bo
AU  - Qiao B
FAU - Zhai, Yuan
AU  - Zhai Y
FAU - Farmer, Douglas G
AU  - Farmer DG
FAU - Busuttil, Ronald W
AU  - Busuttil RW
FAU - Kupiec-Weglinski, Jerzy W
AU  - Kupiec-Weglinski JW
LA  - eng
GR  - R01 AI023847/AI/NIAID NIH HHS/United States
GR  - AI23847/AI/NIAID NIH HHS/United States
GR  - R01 AI042223/AI/NIAID NIH HHS/United States
GR  - R56 AI023847/AI/NIAID NIH HHS/United States
GR  - R01 DK062357/DK/NIDDK NIH HHS/United States
GR  - R21 AI023847/AI/NIAID NIH HHS/United States
GR  - AI42223/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091222
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Chemokine CCL2)
RN  - 0 (E-Selectin)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Pyrimidinones)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Thiazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 89367-92-0 
      (5(4'-hydroxybenzylidenoimino)-3-methylisothiazolo(5,4-d)pyrimidine-(7H)-4,6-dione)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - E-Selectin/metabolism
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Interferon-gamma/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Liver/*metabolism/*pathology
MH  - Macrophages/cytology/metabolism/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pyrimidinones/metabolism
MH  - RNA, Small Interfering
MH  - Reperfusion Injury/*prevention & control
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thiazoles/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC2890105
EDAT- 2009/12/24 06:00
MHDA- 2010/07/31 06:00
PMCR- 2011/05/01
CRDT- 2009/12/24 06:00
PHST- 2009/12/24 06:00 [entrez]
PHST- 2009/12/24 06:00 [pubmed]
PHST- 2010/07/31 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - S1525-0016(16)31034-6 [pii]
AID - 10.1038/mt.2009.285 [doi]
PST - ppublish
SO  - Mol Ther. 2010 May;18(5):1019-25. doi: 10.1038/mt.2009.285. Epub 2009 Dec 22.