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

• Matsubara, Kohki

• Matsushita, Yoshihiro

• Sakai, Kiyoshi

• Kano, Fumiya

• Kondo, Megumi

• Noda, Mariko

• Hashimoto, Noboru

• Imagama, Shiro

• Ishiguro, Naoki

• Suzumura, Akio

• Ueda, Minoru

• Furukawa, Koichi

• Yamamoto, Akihito

抄録

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.

収録刊行物

• The Journal of Neuroscience

  The Journal of Neuroscience 35 (6), 2452-2464, 2015-02

  Society for Neuroscience

キーワード

• anti-inflammation
• dental pulp stem cells
• macrophage polarity
• MCP-1
• Siglec-9
• spinal cord injury

詳細情報

• CRID: 1050282813782391552
• NII論文ID: 120005946848
• DOI: 10.1523/jneurosci.4088-14.2015
• ISSN: 15292401
• ISSN: 02706474
• HANDLE: 2237/25433
• Web Site: https://nagoya.repo.nii.ac.jp/records/23238
• Web Site: https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.4088-14.2015
• 本文言語コード: en
• 資料種別: journal article
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