the glial scar-monocyte interplay a pivotal resolution phase in spinal cord repair神经胶质scar-monocyte相互作用关键的决议阶段脊髓修复.pdfVIP

The Glial Scar-Monocyte Interplay: A Pivotal Resolution Phase in Spinal Cord Repair 1. 1. 1. 2 1 Ravid Shechter , Catarina Raposo , Anat London , Irit Sagi , Michal Schwartz * 1 Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel, 2 Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel Abstract The inflammatory response in the injured spinal cord, an immune privileged site, has been mainly associated with the poor prognosis. However, recent data demonstrated that, in fact, some leukocytes, namely monocytes, are pivotal for repair due to their alternative anti-inflammatory phenotype. Given the pro-inflammatory milieu within the traumatized spinal cord, known to skew monocytes towards a classical phenotype, a pertinent question is how parenchymal-invading monocytes acquire resolving properties essential for healing, under such unfavorable conditions. In light of the spatial association between resolving (interleukin (IL)-10 producing) monocytes and the glial scar matrix chondroitin sulfate proteoglycan (CSPG), in this study we examined the mutual relationship between these two components. By inhibiting the de novo production of CSPG following spinal cord injury, we demonstrated that this extracellular matrix, mainly known for its ability to inhibit axonal growth, serves as a critical template skewing the entering monocytes towards the resolving phenotype. In vitro cell culture studies demonstrated that this matrix alone is sufficient to induce such monocyte polarization. Reciprocal conditional ablation of the monocyte-derived macrophages concentrated at the lesion margins, using diphtheria toxin, reve