PMID- 23994719
OWN - NLM
STAT- MEDLINE
DCOM- 20140709
LR  - 20231213
IS  - 1878-5492 (Electronic)
IS  - 0966-3274 (Linking)
VI  - 29
IP  - 1-4
DP  - 2013 Dec
TI  - The suppression of inflammatory macrophage-mediated cytotoxicity and 
      proinflammatory cytokine production by transgenic expression of HLA-E.
PG  - 76-81
LID - S0966-3274(13)00065-8 [pii]
LID - 10.1016/j.trim.2013.08.001 [doi]
AB  - BACKGROUND: Macrophages participate in xenogenic rejection and represent a major 
      biological obstacle to successful xenotransplantation. The signal inhibitory 
      regulatory protein alpha (SIRPalpha) receptor was reported to be a negative regulator of 
      macrophage phagocytic activity via interaction with CD47, its ligand. Because a 
      majority of human macrophages express the inhibitory receptor CD94/NKG2A, which 
      binds specifically to the human leukocyte antigen (HLA)-E and contains 
      immunoreceptor tyrosine-based inhibition motifs (ITIMs), the inhibitory function 
      of HLA class I molecules, HLA-E, on macrophage-mediated cytolysis was examined. 
      The suppressive effect against proinflammatory cytokine production by macrophages 
      was also examined. METHODS: Complementary DNA (cDNA) of HLA-E, and CD47 were 
      prepared and transfected into swine endothelial cells (SEC). The expression of 
      the modified genes was evaluated by flow cytometry and macrophage-mediated 
      cytolysis was assessed using in vitro generated macrophages. RESULTS: Transgenic 
      expression of HLA-E significantly suppressed the macrophage-mediated 
      cytotoxicity. HLA-E transgenic expression demonstrated a significant suppression 
      equivalent to CD47 transgenic expression. Furthermore, transgenic HLA-E 
      suppressed the production of pro-inflammatory cytokines by inflammatory 
      macrophages. CONCLUSIONS: These results indicate that generating transgenic HLA-E 
      pigs might protect porcine grafts from, not only NK cytotoxicity, but also 
      macrophage-mediated cytotoxicity.
CI  - (c) 2013 Elsevier B.V. All rights reserved.
FAU - Maeda, Akira
AU  - Maeda A
AD  - Department of Surgery, Osaka University Graduate School of Medicine, Osaka, 
      Japan. Electronic address: amaeda@orgtrp.med.osaka-u.ac.jp.
FAU - Kawamura, Takuji
AU  - Kawamura T
FAU - Ueno, Takehisa
AU  - Ueno T
FAU - Usui, Noriaki
AU  - Usui N
FAU - Eguchi, Hiroshi
AU  - Eguchi H
FAU - Miyagawa, Shuji
AU  - Miyagawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130829
PL  - Netherlands
TA  - Transpl Immunol
JT  - Transplant immunology
JID - 9309923
RN  - 0 (CD47 Antigen)
RN  - 0 (CD47 protein, human)
RN  - 0 (Cytokines)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Animals
MH  - CD47 Antigen/genetics/immunology/metabolism
MH  - Cell Line
MH  - Cytokines/biosynthesis/genetics/*immunology
MH  - Endothelial Cells/*immunology/metabolism/pathology
MH  - Gene Expression
MH  - Heterografts
MH  - Histocompatibility Antigens Class I/biosynthesis/genetics/*immunology
MH  - Humans
MH  - Inflammation
MH  - Inflammation Mediators/*immunology/metabolism
MH  - Macrophages/*immunology/metabolism/pathology
MH  - *Organ Transplantation
MH  - Swine
MH  - *Transgenes
MH  - *Transplantation Tolerance
MH  - HLA-E Antigens
OTO - NOTNLM
OT  - HLA-E
OT  - Immunoreceptor tyrosine-based inhibition motif (ITIM)
OT  - Inflammatory macrophage
OT  - Pro-inflammatory cytokine
OT  - Xenocytotoxicity
EDAT- 2013/09/03 06:00
MHDA- 2014/07/10 06:00
CRDT- 2013/09/03 06:00
PHST- 2013/06/15 00:00 [received]
PHST- 2013/08/09 00:00 [revised]
PHST- 2013/08/11 00:00 [accepted]
PHST- 2013/09/03 06:00 [entrez]
PHST- 2013/09/03 06:00 [pubmed]
PHST- 2014/07/10 06:00 [medline]
AID - S0966-3274(13)00065-8 [pii]
AID - 10.1016/j.trim.2013.08.001 [doi]
PST - ppublish
SO  - Transpl Immunol. 2013 Dec;29(1-4):76-81. doi: 10.1016/j.trim.2013.08.001. Epub 
      2013 Aug 29.