Serum from the Human Fracture Hematoma Contains a Potent Inducer of Neutrophil Chemotaxis

Okan W. Bastian*, Mikolaj H. Mrozek, Marco Raaben, Luke P. H. Leenen, Leo Koenderman, Taco J. Blokhuis

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

Abstract

A controlled local inflammatory response is essential for adequate fracture healing. However, the current literature suggests that local and systemic hyper-inflammatory conditions after major trauma induce increased influx of neutrophils into the fracture hematoma (FH) and impair bone regeneration. Inhibiting neutrophil chemotaxis towards the FH without compromising the hosts' defense may therefore be a target of future therapies that prevent impairment of fracture healing after major trauma. We investigated whether chemotaxis of neutrophils towards the FH could be studied in vitro. Moreover, we determined whether chemotaxis of neutrophils towards the FH was mediated by the CXCR1, CXCR2, FPR, and C5aR receptors. Human FHs were isolated during an open reduction internal fixation (ORIF) procedure within 3 days after trauma and spun down to obtain the fracture hematoma serum. Neutrophil migration towards the FH was studied using Ibidi (TM) Chemotaxis(3D) mu-Slides and image analysis of individual neutrophil tracks was performed. Our study showed that the human FH induces significant neutrophil chemotaxis, which was not affected by blocking CXCR1 and CXCR2. In contrast, neutrophil chemotaxis towards the FH was significantly inhibited by chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS), which blocks FPR and C5aR. Blocking only C5aR with CHIPS Delta 1F also significantly inhibited neutrophil chemotaxis towards the FH. Our finding that neutrophil chemotaxis towards the human FH can be blocked in vitro using CHIPS may aid the development of therapies that prevent impairment of fracture healing after major trauma.
Original languageEnglish
Pages (from-to)1084-1092
Number of pages9
JournalInflammation
Volume41
Issue number3
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • fracture
  • neutrophil
  • CHIPS
  • CHIPS Delta 1F
  • C5aR
  • CXCR1/2
  • PLATELET-ACTIVATING-FACTOR
  • INFLAMMATORY RESPONSE
  • STAPHYLOCOCCUS-AUREUS
  • INHIBITORY PROTEIN
  • PEPTIDE RECEPTOR
  • INJURY
  • TRAUMA
  • RATS

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