The crucial role of neutrophil granulocytes in bone fracture healing

Abstract

Delayed bone fracture healing and the formation of non-unions 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 pro- and 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.

Keywords

• Fracture healing
• severe trauma
• thoracic trauma
• inflammation
• neutrophil granulocytes