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. 2022 Jun;48(3):1601-1611.
doi: 10.1007/s00068-021-01703-2. Epub 2021 Jun 10.

Standardized porcine unilateral femoral nailing is associated with changes in PMN activation status, rather than aberrant systemic PMN prevalence

Michel Paul Johan Teuben  1   2   3   4 , Roman Pfeifer  5   6 , Klemens Horst  7 , Tim-Philipp Simon  8 , Marjolein Heeres  9   10 , Yannik Kalbas  5   6 , Taco Blokhuis  11 , Frank Hildebrand  7 , Leo Koenderman  10   12 , Hans-Christoph Pape  5   6 , Luke Leenen  9 ; TREAT-Research Collaboration
Collaborators, Affiliations

Standardized porcine unilateral femoral nailing is associated with changes in PMN activation status, rather than aberrant systemic PMN prevalence

Michel Paul Johan Teuben et al. Eur J Trauma Emerg Surg. 2022 Jun.

Abstract

Purpose: Intramedullary nailing (IMN) of fractures is associated with increased rates of inflammatory complications. The pathological mechanism underlying this phenomenon is unclear. However, polymorphonuclear granulocytes (PMNs) seem to play an important role. We hypothesized that a femur fracture and standardized IMN in pigs is associated with altered appearance of PMNs in circulation and enhanced activation status of these cells.

Methods: A porcine model including a femur fracture and IMN was utilized. Animals were randomized for control [anesthesia + mechanical ventilation only (A/MV)] and intervention [A/MV and unilateral femur fracture (FF) + IMN] conditions. PMN numbers and responsiveness, integrin (CD11b), L-selectin (CD62L) and Fcγ-receptor (CD16 and CD32)-expression levels were measured by flowcytometry of blood samples. Animals were observed for 72 h.

Results: Circulatory PMN numbers did not differ between groups. Early PMN-responsiveness was retained after insult. PMN-CD11b expression increased significantly upon insult and peaked after 24 h, whereas CD11b in control animals remained unaltered (P = 0.016). PMN-CD16 expression levels in the FF + IMN-group rose gradually over time and were significantly higher compared with control animals, after 48 h (P = 0.016) and 72 h (P = 0.032). PMN-CD62L and CD32 expression did not differ significantly between conditions.

Conclusion: This study reveals that a femur fracture and subsequent IMN in a controlled setting in pigs is associated with enhanced activation status of circulatory PMNs, preserved PMN-responsiveness and unaltered circulatory PMN-presence. Indicating that monotrauma plus IMN is a specific and substantial stimulus for the cellular immune system. Early alterations of circulatory PMN receptor expression dynamics may be predictive for the intensity of the post traumatic response.

Keywords: Activation status; Inflammation; Intra-medullary nailing; Polymorphonuclear neutrophils; Porcine modelling.

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Conflict of interest statement

M.T./R.P. have received research grants (as mentioned previously). All other authors (K.H., T.S., T.B., Y.K. F.H., L.K., H.P., L.L. declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a Absolute neutrophil numbers in peripheral blood over time. b Alterations in percentages of PMNs/leukocytes in circulation
Fig. 2
Fig. 2
a Circulatory neutrophil Mac-1 expression changes over time. Receptor expression on neutrophils over time. *P < 0.05. b Circulatory neutrophil L-Selectin expression alterations over time. Receptor expression on neutrophils over time. Data in mean (SD). *P < 0.05, control vs. isolated femur fracture and IMN
Fig. 3
Fig. 3
a Circulatory neutrophil FcyRIII expression alterations over time. b Circulatory neutrophil FcyRII expression alterations over time. Receptor expression on neutrophils over time. Data in mean (SD). *P < 0.05, isolated femur fracture and IMN vs. control
Fig. 4
Fig. 4
PMN-Mac 1 expression following ex vivo LPS-stimulation prior and post instrumentation. Data in mean (SD). *P < 0.05, **P < 0.01, ***P < 0.001
See this image and copyright information in PMC

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