Temporal kinetics of macrophage polarization in the injured rat spinal cord

Abstract

Local activated macrophages derived from infiltrating monocytes play an important role in the damage and repair process of spinal cord injury (SCI). The present study investigates the dynamic change of classically activated proinflammatory (M1) and alternatively activated anti-inflammatory (M2) cells in a rat model with contusive SCI by flow cytometry (FCM) and immunohistochemistry. The macrophage subsets were immunophenotyped by using antibodies against cluster of differentiation (CD)-68, C-C chemokine receptor type 7 (CCR7), CD163, and arginase 1 (Arg1). The CD68(+) CD163(-) and CD68(+) CCR7(+) cells were determined to be M1 subsets, whereas the CD68(+) CD163(+) and CD68(+) Arg1(+) cell subpopulations represented M2 cells. The subsets of macrophages in the injured spinal cord at 1, 3, 5, 7, 14, and 28 days postinjury (dpi) were examined. In the sham-opened spinal cord, few M1 or M2 cells were found. After SCI, the phenotypes of both M1 and M2 cells were rapidly induced. However, M1 cells were detected and maintained at a high level for up to 28 dpi (the longest time evaluated in this study). In contrast, M2 cells were transiently detected at high levels before 7 dpi and returned to preinjury levels at 14 dpi. These results indicate that M1 cell response is rapidly induced and sustained, whereas M2 induction is transient after SCI in rat. Increasing the fraction of M2 cells and prolonging their residence time in the injured local microenvironment is a promising strategy for the repair of SCI.

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

“…The number of M1 macrophages peaks at 5 d, promoting inflammation by activating proinflammatory cytokines such as IL‐1β, IL‐6, and TNF‐α, and apoptosis by ROS production; whereas, the number of M2 macrophages peaks at 14 d, substantially producing IL‐10 to promote axonal regeneration 33. Thus, the directly injected CONPs, when internalized to macrophages, can activate their phenotype more anti‐inflammatory (i.e., more M2 than M1), ultimately promoting axonal regeneration.…”

Sustained release of collagen VI potentiates sciatic nerve regeneration by modulating macrophage phenotype

“…These M1 macrophages produce bactericidal and neurotoxic chemicals such as reactive oxygen species, reactive nitrogen species, TNF‐α and proteases, which not only promote resistance to pathogens and tumor cells but may also harm the neurons and glial cells. Conversely, macrophages can be induced to adopt the M2 phenotype by IL‐4, IL‐13 and macrophage colony‐stimulating factor (M‐CSF) and promote wound healing, immune regulation and vascularization (Chen et al ., ; Alvarez et al ., ). They are regarded as anti‐inflammatory macrophages and produce IL‐10 and IL‐5.…”

Temporal kinetics of CD8+CD28+ and CD8+CD28− T lymphocytes in the injured rat spinal cord

“…This may be related to the inflammatory process in the secondary injury after SCI (Chaitanya et al, ; Mueller et al, ). In addition to cytotoxic CD8 + T cells, some other cells that are not conducive to the repair of SCI, such as Th1 and M1 cells, were also dominant in the injured site (Chen et al, ; Hu et al, ). These suggest that under natural conditions, the local immune microenvironment is not conducive to repair.…”

“…Cell quantification of spinal cord tissue was performed using the ImageJ Software (http://rsb.info.nih.gov/ij/; RRID: nif‐0000‐10512; National Institutes of Health) as mentioned earlier (Chen et al, ; Drury et al, ). The spinal cord cross‐sections from eight rats per time‐point were used for evaluation.…”