¸ñÀû: Chronic rhinosinusitis with nasal polyps (CRSwNP) includes very diverse
inflammatory cells, which are thought to play an important role in
CRSwNP pathophysiology. However, neutrophils remain elusive cells in
CRSwNP. This study was performed to investigate the functional changes
of neutrophils in response to inflammatory stimuli. ¹æ¹ý:Bloods and nasal tissues were collected from patients with CRSwNP and
control subjects. Type 2 and non-type 2 CRSwNP were classified based on
blood counts of eosinophils (greater or lesser than 250 cells/¥ìL).
Tissue neutrophils (TN) and blood neutrophils (BN) were stimulated with
lipopolysaccharide (LPS) and IL-4. After the stimulation, the
supernatants were collected and the protein levels of various
inflammatory cytokines and several typical N1 (CCL3, CXCL9, CXCL10,
Fas/CD95) and N2 (CCL2, CCL5, MMP9, VEGF) markers were measured using
multiplex immunoassays. °á°ú:The expression levels of N1-related proteins (CCL3, CXCL9, and
Fas/CD95) were and N2-related proteins (CCL2, MMP9, and VEGF) were
also all significantly higher in LPS-treated BN, regardless of
endotype. In LPS-treated TN of type 2 and non-type 2 CRSwNP, the N1
marker Fas/CD95 and N2 marker CCL2 were significantly decreased.
However, another N1 marker CXCL9 was significantly decreased,
especially in type 2 CRSwNP. Inflammatory cytokine levels (IL-1¥â, IL-
6, IL-8/CXCL8, IL-17A, IL-23, IL-33 and TNF-¥á) were found to be
significantly higher in LPS-treated BN, regardless of endotype. IL-10
was significantly increased in control and type2 CRSwNP. Consistent
with LPS-treated BN, TNF-¥á, IL-6 and IL-8/CXCL8 were significantly
increased in TN. In LPS-treated TN of type 2 and non-type 2 CRSwNP,
the IL-17A was significantly decreased and TGF-¥â was significantly
increased. IL-10 and IL-12p70 were significantly decreased in LPS-
treated TN of type 2 CRSwNP. In addition, N2 markers (CCL2 and CCL5)
were significantly increased and IL-13 and IFN¥ã were all
significantly decreased in IL-4-treated BN regardless of endotype. N2
marker (MMP9), IL-17A and IL-18 were significantly decreased in IL-4-
treated BN of type 2 CRSwNP. IL-4-treated TN showed higher expression
levels of the CCL5 (N2) in type 2 and non-type 2 CRSwNP. IL-33 was
significantly increased in IL-4-treated TN of type 2 CRSwNP. °á·Ð:This study indicate that neutrophils perform various functional roles
based on their location and stimuli, exhibiting diminished protective
functions in type 2 inflammatory conditions. |