PMID- 25673840
OWN - NLM
STAT- MEDLINE
DCOM- 20150413
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 35
IP  - 6
DP  - 2015 Feb 11
TI  - Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte 
      chemoattractant protein-1 promote recovery after rat spinal cord injury by 
      altering macrophage polarity.
PG  - 2452-64
LID - 10.1523/JNEUROSCI.4088-14.2015 [doi]
AB  - Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support 
      recovery from neural insults via paracrine mechanisms that are poorly understood. 
      Here we show that the conditioned serum-free medium (CM) from SHEDs, administered 
      intrathecally into rat injured spinal cord during the acute postinjury period, 
      caused remarkable functional recovery. The ability of SHED-CM to induce recovery 
      was associated with an immunoregulatory activity that induced anti-inflammatory 
      M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously 
      unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte 
      chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic 
      acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from 
      the SHED-CM prominently reduced its ability to induce M2-like macrophages and to 
      promote functional recovery after spinal cord injury (SCI). The combination of 
      MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of 
      bone marrow-derived macrophages in vitro, and this effect was abolished by a 
      selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic 
      knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the 
      injured spinal cord induced M2-like macrophages and led to a marked recovery of 
      hindlimb locomotor function after SCI. The inhibition of this M2 induction 
      through the inactivation of CCR2 function abolished the therapeutic effects of 
      both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and 
      ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar 
      granule neurons against the neurotoxic effects of chondroitin sulfate 
      proteoglycans. Our data suggest that the unique combination of MCP-1 and 
      ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage 
      induction.
CI  - Copyright (c) 2015 the authors 0270-6474/15/352452-13$15.00/0.
FAU - Matsubara, Kohki
AU  - Matsubara K
AD  - Department of Oral and Maxillofacial Surgery.
FAU - Matsushita, Yoshihiro
AU  - Matsushita Y
AUID- ORCID: 0000-0001-7447-061X
AD  - Department of Oral and Maxillofacial Surgery.
FAU - Sakai, Kiyoshi
AU  - Sakai K
AD  - Department of Oral and Maxillofacial Surgery.
FAU - Kano, Fumiya
AU  - Kano F
AD  - Department of Oral and Maxillofacial Surgery.
FAU - Kondo, Megumi
AU  - Kondo M
AD  - Department of Oral and Maxillofacial Surgery.
FAU - Noda, Mariko
AU  - Noda M
AUID- ORCID: 0000-0002-6066-1359
AD  - Department of Neuroimmunology, Research Institute of Environmental Medicine, 
      Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
FAU - Hashimoto, Noboru
AU  - Hashimoto N
AD  - Biochemistry II, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 
      466-8550, Japan, and.
FAU - Imagama, Shiro
AU  - Imagama S
AD  - Orthopedic Surgery, and.
FAU - Ishiguro, Naoki
AU  - Ishiguro N
AD  - Orthopedic Surgery, and.
FAU - Suzumura, Akio
AU  - Suzumura A
AD  - Department of Neuroimmunology, Research Institute of Environmental Medicine, 
      Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
FAU - Ueda, Minoru
AU  - Ueda M
AD  - Department of Oral and Maxillofacial Surgery.
FAU - Furukawa, Koichi
AU  - Furukawa K
AD  - Biochemistry II, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 
      466-8550, Japan, and.
FAU - Yamamoto, Akihito
AU  - Yamamoto A
AD  - Department of Oral and Maxillofacial Surgery, akihito@med.nagoya-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Antigens, CD)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, CCR2)
RN  - 0 (SIGLEC9 protein, human)
RN  - 0 (Sialic Acid Binding Immunoglobulin-like Lectins)
SB  - IM
MH  - Animals
MH  - Antigens, CD/metabolism/*pharmacology
MH  - Blood-Brain Barrier/drug effects
MH  - Brain Injuries/drug therapy
MH  - Cell Polarity/drug effects
MH  - Cerebellum/cytology/drug effects/metabolism
MH  - Chemokine CCL2/metabolism/*pharmacology
MH  - Child
MH  - Culture Media, Conditioned
MH  - Cytokines/metabolism
MH  - Dental Pulp/cytology/metabolism
MH  - Humans
MH  - Macrophages/*drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, CCR2/antagonists & inhibitors
MH  - Sialic Acid Binding Immunoglobulin-like Lectins/metabolism/*pharmacology
MH  - Spinal Cord Injuries/*drug therapy/pathology
MH  - Tooth, Deciduous
PMC - PMC6605605
OTO - NOTNLM
OT  - MCP-1
OT  - Siglec-9
OT  - anti-inflammation
OT  - dental pulp stem cells
OT  - macrophage polarity
OT  - spinal cord injury
EDAT- 2015/02/13 06:00
MHDA- 2015/04/14 06:00
PMCR- 2015/08/11
CRDT- 2015/02/13 06:00
PHST- 2015/02/13 06:00 [entrez]
PHST- 2015/02/13 06:00 [pubmed]
PHST- 2015/04/14 06:00 [medline]
PHST- 2015/08/11 00:00 [pmc-release]
AID - 35/6/2452 [pii]
AID - 4088-14 [pii]
AID - 10.1523/JNEUROSCI.4088-14.2015 [doi]
PST - ppublish
SO  - J Neurosci. 2015 Feb 11;35(6):2452-64. doi: 10.1523/JNEUROSCI.4088-14.2015.