Your browser doesn't support javascript.
loading
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.
Afiliação
  • Matsubara K; Department of Oral and Maxillofacial Surgery.
  • Matsushita Y; Department of Oral and Maxillofacial Surgery.
  • Sakai K; Department of Oral and Maxillofacial Surgery.
  • Kano F; Department of Oral and Maxillofacial Surgery.
  • Kondo M; Department of Oral and Maxillofacial Surgery.
  • Noda M; Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
  • Hashimoto N; Biochemistry II, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan, and.
  • Imagama S; Orthopedic Surgery, and.
  • Ishiguro N; Orthopedic Surgery, and.
  • Suzumura A; Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
  • Ueda M; Department of Oral and Maxillofacial Surgery.
  • Furukawa K; Biochemistry II, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan, and.
  • Yamamoto A; Department of Oral and Maxillofacial Surgery, akihito@med.nagoya-u.ac.jp.
J Neurosci ; 35(6): 2452-64, 2015 Feb 11.
Article em En | MEDLINE | ID: mdl-25673840
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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismos da Medula Espinal / Antígenos CD / Quimiocina CCL2 / Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico / Macrófagos Limite: Animals / Child / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Traumatismos da Medula Espinal / Antígenos CD / Quimiocina CCL2 / Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico / Macrófagos Limite: Animals / Child / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article