Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation.

نویسندگان

  • René Köffel
  • Anastasia Meshcheryakova
  • Joanna Warszawska
  • Annika Hennig
  • Karin Wagner
  • Almut Jörgl
  • Daniela Gubi
  • Doris Moser
  • Anastasiya Hladik
  • Ulrike Hoffmann
  • Michael B Fischer
  • Wim van den Berg
  • Marije Koenders
  • Clemens Scheinecker
  • Bernhard Gesslbauer
  • Sylvia Knapp
  • Herbert Strobl
چکیده

During inflammation, neutrophils are rapidly mobilized from the bone marrow storage pool into peripheral blood (PB) to enter lesional sites, where most rapidly undergo apoptosis. Monocytes constitute a second wave of inflammatory immigrates, giving rise to long-lived macrophages and dendritic cell subsets. According to descriptive immunophenotypic and cell culture studies, neutrophils may directly "transdifferentiate" into monocytes/macrophages. We provide mechanistic data in human and murine models supporting the existence of this cellular pathway. First, the inflammatory signal-induced MKK6-p38MAPK cascade activates a monocyte differentiation program in human granulocyte colony-stimulating factor-dependent neutrophils. Second, adoptively transferred neutrophils isolated from G-CSF-pretreated mice rapidly acquired monocyte characteristics in response to inflammatory signals in vivo. Consistently, inflammatory signals led to the recruitment of osteoclast progenitor cell potential from ex vivo-isolated G-CSF-mobilized human blood neutrophils. Monocytic cell differentiation potential was retained in left-shifted band-stage neutrophils but lost in neutrophils from steady-state PB. MKK6-p38MAPK signaling in HL60 model cells led to diminishment of the transcription factor C/EBPα, which enabled the induction of a monocytic cell differentiation program. Gene profiling confirmed lineage conversion from band-stage neutrophils to monocytic cells. Therefore, inflammatory signals relayed by the MKK6-p38MAPK cascade induce monocytic cell differentiation from band-stage neutrophils.

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عنوان ژورنال:
  • Blood

دوره 124 17  شماره 

صفحات  -

تاریخ انتشار 2014