title: No major role for the transcription factor NF-κB in bone marrow function during peritonitis in the mouse.
abstract: Nuclear factor-kappa B (NF-κB) is a multipotent transcription factor that plays a pivotal role in immune reactions, inflammation, and possibly hematopoiesis as well. Mobilization of neutrophilic granulocytes during inflammation is a highly regulated process, but one that is incompletely understood. We studied the in vivo activity of NF-κB in mouse organs and cells, with a focus on bone marrow, during acute inflammation. NF-κB activity was studied in transgenic mice expressing a luciferase reporter expressed in a NF-κB activation-dependent fashion. Acute peritoneal inflammation was induced by lipopolysaccharide (LPS), the casein digest bacto-tryptone, or the insoluble polysaccharide zymosan. Organs were removed and blood, bone marrow, and peritoneal cells were separated using density gradient centrifugation. NF-κB activity in organ homogenates and cell lysates was quantified. These three inflammatory agents increased NF-κB activity to a variable extent within the inflamed peritoneal cavity, liver, and spleen, with LPS being the strongest stimulus. LPS, but not bacto-tryptone or zymosan, activated NF-κB in lung and bone marrow, the latter activity mainly observed in density fractions rich in immature bone marrow cells. NF-κB activation was prominent at 6 h after induction of peritonitis, fading at 24 h, as expected for an acute phase phenomenon. From this proof-of-principle study with luciferase reporter mice dependent on NF-κB activation, we suggest that, in steady-state mice, mobilization of bone marrow granulocytes to an inflammatory site can occur without discernible activation of NF-κB in bone marrow.
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Eirunn
authors.initials: E
authors.lastname: Knudsen
authors.forename: Harald
authors.initials: H
authors.lastname: Carlsen
authors.forename: Arne
authors.initials: A
authors.lastname: Bøyum
authors.forename: Haakon Breien
authors.initials: HB
authors.lastname: Benestad
authors.forename: Per Ole
authors.initials: PO
authors.lastname: Iversen
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology / Q000473:pathology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010461:Peptones; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D015054:Zymosan
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D010461:Peptones; C030846:Bacto-peptone; D015054:Zymosan; D008156:Luciferases