Local exposure of bone components to injured soft tissue induces Toll-like receptor 4-dependent systemic inflammation with acute lung injury

Philipp Kobbe*, David J. Kaczorowski, Yoram Vodovotz, Christopher H. Tzioupis, Kevin P. Mollen, Timothy R. Billiar, Hans Christoph Pape

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Remote and systemic inflammatory responses after long bone fractures have been well described, but the mechanisms underlying these changes remain unexplained. We hypothesized that bone components locally exposed to injured soft tissue are capable of inducing a systemic inflammatory response associated with acute lung injury, and that this inflammatory cascade requires Toll-like receptor 4 (TLR-4) signaling. Accordingly, male C3H/HeOuJ (TLR- 4-competent) and C3H/HeJ (TLR-4-mutant) mice were injected with various bone components (bone marrow cells, bone marrow supernatant, and bone suspension, respectively) in bilaterally injured thigh muscles and euthanized after 6 h. Serum TNF-α, IL-6, and IL-10 levels, and pulmonary myeloperoxidase activity was measured using specific enzyme-linked immunosorbent assay kits. Pulmonary permeability changes were assessed with bronchoalveolar lavage. Local exposure of bone components to injured soft tissue induced systemic inflammation and acute lung injury in TLR-4-competent, but not in TLR-4-mutant, animals. These findings suggest that bone components contribute to systemic inflammation and acute lung injury after long bone fractures via TLR-4 signaling and support the notion of a central role for TLR-4 in sensing tissue damage.

Original languageEnglish
Pages (from-to)686-691
Number of pages6
JournalShock
Volume30
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Keywords

  • Bone marrow
  • Long bone fracture
  • Multiple organ failure
  • Pseudofracture model
  • Soft tissue injury
  • Toll-like receptor 4

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