| Background:Local inflammatory response after spinal cord injury is an immune-initiated repair process.Major participants in this process include neutrophils,mononuclear macrophages in the blood,microglia,and T cells.Macrophages are the main participants in this process with the longest duration and the largest number of participants.After the occurrence of spinal cord injury,inflammatory cytokines,chemokines and myelin sheath fragments produced in the acute stage of injury form an inflammatory environment,and microglia cells and mononuclear macrophages are recruited to enter the local area of injury to remove myelin sheath fragments produced by injury,and further secrete inflammatory cytokines and chemokines to promote the removal of injury fragments.Inflammatory factors and ROS produced during macrophage activation and phagocytosis will further damage the surrounding normal nerve tissue,and then produce more fragments,which is the process of secondary injury.The occurrence of secondary injury causes the continuous activation of macrophages to form a continuous inflammatory environment,which in turn hinders the transition of inflammatory response to the repair process,and the excessive proliferation of scar tissue,which in turn hinders the repair process after spinal cord injury.How to accelerate the removal of myelin sheath fragments by macrophages into the repair period and reduce the secondary injury may be a new idea for the treatment of spinal cord injury.CD47 is a widely found transmembrane protein on the surface of normal cells.Its molecular weight is about 50 k Da,and it belongs to the immunoglobulin superfamily.Plays an important role in the nervous and immune systems.There are three known natural ligands for CD47: integrin,platelet agglutinin-1 and SIRP?,among which the CD47-SIRP-a signaling pathway is an important signaling pathway that regulates macrophage phagocytosis.Studies have shown that the high expression of CD47 is an important mechanism to inhibit the phagocytosis of macrophages,and the flight of the seed in tumor immunity is closely related to the formation of foam cells in atherosclerosis,and the application of CD47 antibody can reduce the formation of foam cells in atherosclerosis and destroy the emergence of tumor immune escape.In this study,we assumed that CD47-SIRP-a signaling pathway could promote macrophage phagocytosis and clearance of myelin sheath fragments after spinal cord injury,thus reducing the occurrence of secondary injury,breaking the inflammatory environment of macrophage continuous activation,and promoting the recovery of neurological function after injury.Objective:To investigate the effects of blocking CD47-SIRP-a signaling pathway on inflammatory response and neurological function recovery after spinal cord injury in miceMethods:Immunofluorescence staining was used to observe the distribution of microglial cells and monocyte derived macrophages in the spinal cord of mice.The expression of CD47 was measured by immunofluorescence staining and WB after spinal cord injury.The changes of inflammatory cytokines(TNF-a IL-1b)after spinal cord injury were measured by q-PCR and immunofluorescence staining.Immunofluorescence staining was used to observe the changes of local macrophage functional typing after spinal cord injury.The number and source of macrophages after spinal cord injury were measured by flow cytometry.Immunofluorescence staining was used to observe the size of scar and the formation of foam cells after spinal cord injury.The neurological function recovery of WT mice treated with CD47 blocking antibody was measured by behavioral experiment.Results:(A)Blocking the CD47-SIRP-a signaling pathway can promote phagocytosis of macrophages to myelin debris(B)Blockage of CD47-SIRP-a signaling pathway can promote the chemotaxis of macrophages into the damaged area,and the absolute number of macrophages in the damaged area increases,and part of the increase comes from monocytes in the blood.(C)Blocking the CD47-SIRP-a signaling pathway can reduce the level of inflammatory cytokines(TNF-A IL-1B)after injury(D)Blocking the CD47-SIRP-a signaling pathway can reduce the formation of foam cells(E)Blocking the CD47-SIRP-a signaling pathway can reduce scar area(F)Blocking the CD47-SIRP-a signaling pathway can promote the recovery of neural function in mice with spinal cord injuryConclusions:CD47-SIRP-A signaling pathway is involved in the repair process after spinal cord injury by regulating phagocytosis of macrophages,blocking this signaling pathway can promote macrophages to phagocytosis of myelin sheath fragments,reduce the level of inflammatory factors after injury,and improve neurological recovery after spinal cord injury to a certain extent. |
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