In mouse models of acute motor axonal neuropathy, anti‐ganglioside antibodies (AGAbs) bind to motor axons, notably the distal nerve, and activate the complement cascade. While complement activation is well studied in this model, the role of inflammatory cells is unknown. Herein we aimed to investigate the contribution of phagocytic cells including macrophages, neutrophils and perisynaptic Schwann cells (pSCs) to distal nerve pathology. To observe this, we first created a subacute injury model of sufficient duration to allow inflammatory cell recruitment. Mice were injected intraperitoneally with an anti‐GD1b monoclonal antibody that binds strongly to mouse motor nerve axons. Subsequently, mice received normal human serum as a source of complement. Dosing was titrated to allow humane survival of mice over a period of 3 days, yet still induce the characteristic neurological impairment. Behaviour and pathology were assessed in vivo using whole‐body plethysmography and post‐sacrifice by immunofluorescence and flow cytometry. ex vivo nerve‐muscle preparations were used to investigate the acute phagocytic role of pSCs following distal nerve injury. Following complement activation at distal intramuscular nerve sites in the diaphragm macrophage localisation or numbers are not altered, nor do they shift to a pro‐ or anti‐inflammatory phenotype. Similarly, neutrophils are not significantly recruited. Instead, ex vivo nerve‐muscle preparations exposed to AGAb plus complement reveal that pSCs rapidly become phagocytic and engulf axonal debris. These data suggest that pSCs, rather than inflammatory cells, are the major cellular vehicle for axonal debris clearance following distal nerve injury, in contrast to larger nerve bundles where macrophage‐mediated clearance predominates.

中文翻译：

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吉兰-巴利综合征小鼠模型中突触周围雪旺细胞吞噬神经末梢碎片。

在急性运动轴突神经病小鼠模型中，抗神经节苷脂抗体（AGAb）与运动轴突（尤其是远端神经）结合，并激活补体级联反应。虽然补体激活在该模型中得到了充分研究，但炎症细胞的作用尚不清楚。在此，我们的目的是研究巨噬细胞、中性粒细胞和突触周围雪旺细胞（pSC）等吞噬细胞对远端神经病理学的贡献。为了观察这一点，我们首先创建了一个足够持续时间的亚急性损伤模型，以允许炎症细胞募集。小鼠腹腔注射抗 GD1b 单克隆抗体，该抗体与小鼠运动神经轴突强烈结合。随后，小鼠接受正常人血清作为补体来源。剂量逐渐调整，使小鼠能够人道地生存 3 天，但仍会引起特征性的神经损伤。使用全身体积描记法对体内行为和病理学进行评估，并通过免疫荧光和流式细胞术进行处死后评估。离体神经肌肉制剂用于研究远端神经损伤后 pSC 的急性吞噬作用。膈肌远端肌内神经部位的补体激活后，巨噬细胞的定位或数量没有改变，也没有转变为促炎或抗炎表型。同样，中性粒细胞也没有大量募集。相反，暴露于 AGAb 加补体的离体神经肌肉制剂显示，pSC 迅速变成吞噬细胞并吞噬轴突碎片。这些数据表明，pSC，而不是炎症细胞，是远端神经损伤后清除轴突碎片的主要细胞载体，而较大的神经束则以巨噬细胞介导的清除为主。