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The concept of plasticity of neutrophils is highlighted by studies showing
their ability to transdifferentiate into antigen-presenting cells. In this
regard, transdifferentiated neutrophils were found at inflammatory sites
of autoimmune arthritis (AIA). Exposure of neutrophils to inflammatory
stimuli prolongs their survival, thereby favoring the acquisition of
pathophysiologically relevant phenotypes and functions. By using
microarrays, qRT-PCR, and ELISAs, we showed that long-lived (LL)
neutrophils obtained after 48 h of culture in the presence of GM-CSF, TNF,
and IL-4 differentially expressed genes related to apoptosis, MHC class
II, immune response, and inflammation. The expression of anti-inflammatory
genes mainly of peptidase inhibitor families is upregulated in LL
neutrophils. Among these, the PI3 gene encoding elafin was the most highly
expressed. The de novo production of elafin by LL neutrophils depended on
a synergism between GM-CSF and TNF via the activation and cooperativity of
CCAAT/enhancer-binding protein ß and NF-κB pathways, respectively. Elafin
concentrations were higher in synovial fluids (SF) of patients with AIA
than in SF of osteoarthritis. SF neutrophils produced more elafin than
blood counterparts. These results are discussed with respect to
implications of neutrophils in chronic inflammation and the potential
influence of elafin in AIA.
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