PMID- 28272428
OWN - NLM
STAT- MEDLINE
DCOM- 20181127
LR  - 20190109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Mar 8
TI  - Secreted Ectodomain of SIGLEC-9 and MCP-1 Synergistically Improve Acute Liver 
      Failure in Rats by Altering Macrophage Polarity.
PG  - 44043
LID - 10.1038/srep44043 [doi]
LID - 44043
AB  - Effective treatments for acute liver failure (ALF) are still lacking. We recently 
      reported that a single intravenous administration of serum-free conditioned 
      medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) 
      into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. 
      However, the specific factors in SHED-CM that are responsible for resolving ALF 
      remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 
      macrophage inducers-monocyte chemoattractant protein-1 (MCP-1) and the secreted 
      ectodomain of sialic acid-binding Ig-like lectin-9 (sSiglec-9)-abolished its 
      ability to resolve rat ALF. Furthermore, treatment with MCP-1/sSiglec-9 alone 
      dramatically improved the survival of ALF rats. This treatment induced 
      anti-inflammatory M2, suppressed hepatocyte apoptosis, and promoted hepatocyte 
      proliferation. Treatment with an M2-depletion reagent (mannosylated clodronate 
      liposomes) suppressed the recovery. In addition, MCP-1 and sSiglec-9 
      synergistically promoted the M2 differentiation of bone marrow-derived 
      macrophages via CCR2, accompanied by the production of multiple 
      liver-regenerating factors. The conditioned medium from MCP-1/sSiglec-9-activated 
      M2 macrophages, but not from interleukin-4-induced ones, suppressed the D-Gal- 
      and LPS-induced apoptosis of primary hepatocytes and promoted their proliferation 
      in vitro. The unique combination of MCP-1/sSiglec-9 ameliorates rat ALF by 
      inhibiting hepatocellular apoptosis and promoting liver regeneration through the 
      induction of anti-inflammatory/tissue-repairing M2 macrophages.
FAU - Ito, Takanori
AU  - Ito T
AD  - Department of Gastroenterology and Hepatology, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Ishigami, Masatoshi
AU  - Ishigami M
AD  - Department of Gastroenterology and Hepatology, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Matsushita, Yoshihiro
AU  - Matsushita Y
AD  - Department of Oral and Maxillofacial Surgery of Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Hirata, Marina
AU  - Hirata M
AD  - Department of Oral and Maxillofacial Surgery of Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Matsubara, Kohki
AU  - Matsubara K
AD  - Department of Oral and Maxillofacial Surgery of Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ishikawa, Tetsuya
AU  - Ishikawa T
AD  - Department of Gastroenterology and Hepatology, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Hibi, Hideharu
AU  - Hibi H
AD  - Department of Oral and Maxillofacial Surgery of Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Ueda, Minoru
AU  - Ueda M
AD  - Department of Oral and Maxillofacial Surgery of Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
FAU - Hirooka, Yoshiki
AU  - Hirooka Y
AD  - Department of Gastroenterology and Hepatology, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Goto, Hidemi
AU  - Goto H
AD  - Department of Gastroenterology and Hepatology, 65 Tsurumai-cho, Showa-ku, Nagoya 
      466-8550, Japan.
FAU - Yamamoto, Akihito
AU  - Yamamoto A
AD  - Department of Oral and Maxillofacial Surgery of Nagoya University Graduate School 
      of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
AD  - Department of Oral histology, Institute of Biomedical Science, Tokushima 
      University Graduate School, 3-18-5 Kuramoto-cho, Tokushima 770-8504, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170308
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Sialic Acid Binding Immunoglobulin-like Lectins)
RN  - 0 (Siglec-9 protein, rat)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Proliferation
MH  - Chemokine CCL2/*metabolism
MH  - Culture Media, Serum-Free
MH  - Female
MH  - Inflammation/complications/metabolism
MH  - Liver Failure, Acute/complications/*metabolism
MH  - Macrophages/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Sialic Acid Binding Immunoglobulin-like Lectins/*metabolism
MH  - Stem Cells/physiology
MH  - Tooth Exfoliation
MH  - Tooth, Deciduous/cytology
PMC - PMC5358744
COIS- The authors declare no competing financial interests.
EDAT- 2017/03/09 06:00
MHDA- 2018/11/28 06:00
PMCR- 2017/03/08
CRDT- 2017/03/09 06:00
PHST- 2016/09/28 00:00 [received]
PHST- 2017/02/01 00:00 [accepted]
PHST- 2017/03/09 06:00 [entrez]
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2018/11/28 06:00 [medline]
PHST- 2017/03/08 00:00 [pmc-release]
AID - srep44043 [pii]
AID - 10.1038/srep44043 [doi]
PST - epublish
SO  - Sci Rep. 2017 Mar 8;7:44043. doi: 10.1038/srep44043.