THE CRUCIAL ROLE OF NEUTROPHIL GRANULOCYTES IN BONE FRACTURE HEALING
THE CRUCIAL ROLE OF NEUTROPHIL GRANULOCYTES IN BONE FRACTURE HEALING
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DOI：
10.22203/ecm.v032a10
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发表时间：
2016-07-01
影响因子：
3.1
通讯作者：
Ignatius, A.
中科院分区：
文献类型：
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作者：
Kovtun, A.;Bergdolt, S.;Ignatius, A.
延迟骨折愈合和骨不连的形成代表了一个重要的临床问题，特别是在遭受创伤后全身炎症的多发伤患者中。然而，潜在的病理机制仍不清楚。中性粒细胞是全身免疫应答中至关重要的效应细胞，并代表早期骨折血肿中最丰富的免疫细胞群。在此，我们研究了中性粒细胞在单纯骨折愈合和由额外胸部创伤诱导的骨折愈合受损的小鼠模型中的作用。在损伤前24小时，用抗-Ly-6 G-抗体全身治疗50%的小鼠以减少嗜中性粒细胞数目。在分离的骨折模型中，Ly-6 G-Ab治疗显著增加了骨折血肿中促炎和抗炎细胞因子的浓度，包括白细胞介素（IL）-6和IL-10，以及趋化因子，例如C-X-C基序配体1（CXCL 1）和单核细胞趋化蛋白-1（MCP-1）。单核细胞/巨噬细胞募集也显著增强。21天后，骨再生明显受损，表现为骨含量显著减少和骨折骨痂机械性能受损。这些结果表明，骨折后炎症阶段中性粒细胞的募集和功能不受干扰对于启动导致骨再生的下游反应至关重要。在复合创伤模型中，中性粒细胞数量的减少改善了肺部炎症，但对骨再生没有任何显著影响，表明中性粒细胞可能在额外胸部创伤诱导的骨折愈合受损中不起关键的病理机制作用。
Delayed bone fracture healing and the formation of nonunions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both proand anti-inflammatory cytokines, including interleukin ( IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma.