Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Köffel, R; Meshcheryakova, A; Warszawska, J; Hennig, A; Wagner, K; Jörgl, A; Gubi, D; Moser, D; Hladik, A; Hoffmann, U; Fischer, MB; van den Berg, W; Koenders, M; Scheinecker, C; Gesslbauer, B; Knapp, S; Strobl, H.
Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions via MKK6 activation.
Blood. 2014; 124(17):2713-2724
Doi: 10.1182/blood-2014-07-588178
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- Führende Autor*innen der Med Uni Graz
- Strobl Herbert
- Co-Autor*innen der Med Uni Graz
- Wagner Karin
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- Abstract:
- 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. © 2014 by The American Society of Hematology.
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