title: Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model.
abstract: The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma.
authors: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany. paula.hoff@charite.de
authors: Paula
authors: P
authors: Hoff
authors: Patrick
authors: P
authors: Maschmeyer
authors: Timo
authors: T
authors: Gaber
authors: Tabea
authors: T
authors: Schütze
authors: Tobias
authors: T
authors: Raue
authors: Katharina
authors: K
authors: Schmidt-Bleek
authors: René
authors: R
authors: Dziurla
authors: Saskia
authors: S
authors: Schellmann
authors: Ferenz Leonard
authors: FL
authors: Lohanatha
authors: Eric
authors: E
authors: Röhner
authors: Andrea
authors: A
authors: Ode
authors: Gerd-Rüdiger
authors: GR
authors: Burmester
authors: Georg N
authors: GN
authors: Duda
authors: Carsten
authors: C
authors: Perka
authors: Frank
authors: F
authors: Buttgereit
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004734:Energy Metabolism / Q000276:immunology*; D005260:Female; D005269:Femur / Q000601:surgery; D050723:Fractures, Bone / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006406:Hematoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma
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