The impact of intramedullary nailing on the characteristics of the pulmonary neutrophil pool in rodents

Int Orthop. 2020 Mar;44(3):595-602. doi: 10.1007/s00264-019-04419-6. Epub 2020 Jan 3.

Abstract

Purpose: Dysregulation of polymorphonuclear neutrophil (PMN) biology is associated with the development of inflammatory complications after trauma, such as acute respiratory distress syndrome (ARDS). It has been demonstrated that intramedullary nailing is both associated with altered pulmonary neutrophil deposition and the occurrence of ARDS. This standardized study aimed to characterize the long-term remote neutrophil response in the lungs in case of a femur fracture and intramedullary nailing.

Methods: A standardized rat model including intramedullary nailing and a femur fracture was utilized. Groups were terminated after observation times of three, seven and 14 days. Neutrophils were isolated from lung parenchyma and broncho-alveolar lavage fluid (BALF) and analyzed by flow cytometry. Absolute neutrophil numbers as well as membrane expression levels of CD11b, CD62L, and CD11a were compared.

Results: Pulmonary neutrophil numbers were increased 3 days after intervention. Membrane expression levels of CD11b (P < 0.01), CD62L (P < 0.01), and CD11a (P = 0.06) on parenchymal PMNs increased as well after 3 days. Thereafter, values restored gradually to physiological levels. Furthermore, neutrophil activation status patterns between parenchymal and BALF neutrophil pools did not correlate.

Conclusions: The current study demonstrates that IMN and a femur fracture are associated with transient increased pulmonary PMN deposition, as well as a specific pattern of activation characterized by temporary increased selectin and integrin receptor expression on pulmonary neutrophils. This phenomenon might play an important role in the pathomechanism of ARDS after IMN. Moreover, we found striking differences between parenchymal and BALF-neutrophil populations, demonstrating the limited readout potential of BALF analysis to investigate the entire pulmonary neutrophil pool.

Keywords: ARDS; Intramedullary nailing; Lung; Neutrophil; Organ failure; Pulmonary immune response.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology*
  • CD11 Antigens / analysis
  • CD11 Antigens / biosynthesis
  • CD11 Antigens / immunology
  • Cell Count
  • Disease Models, Animal
  • Female
  • Femoral Fractures / immunology*
  • Femoral Fractures / surgery*
  • Fracture Fixation, Intramedullary / adverse effects*
  • Inflammation / immunology*
  • L-Selectin / biosynthesis
  • L-Selectin / immunology
  • Lung / immunology*
  • Neutrophils / immunology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • CD11 Antigens
  • L-Selectin