Abstract
Background : Resolution of inflammation is now recognized as a
tightly regulated and active process. Lipoxins (LX) are lead members of
a larger family of specialized pro-resolving mediators with unique
anti-inflammatory and pro-resolving properties. Recent studies
implicated natural killer (NK) cells in the resolution of allergic
airway inflammation, notably in promoting eosinophil apoptosis. The aim
of the study was to better understand the pro-resolving actions of NK
cells and LXA4 during allergic eosinophilic airway
inflammation.
Methods: 20 subjects with grass pollen allergic rhinitis were
included. A nasal provocation test with either a single grass pollen
allergen threshold dose or diluent was used. Nasal lavage fluid and
cells were collected at baseline and at different time points after
challenge. For in vitro assays, eosinophils were incubated with
NK cells.
Results : We observed that NK cells were recruited to the nasal
mucosa shortly after the initiation of the allergic inflammatory
response. This recruitment correlated with eosinophilic inflammation.In vitro assays demonstrated that direct contact and a combined
action of CD56bright and CD56dim NK
cells were needed to promote autologous eosinophil apoptosis. We
furthermore observed that local LXA4 production
correlated with the peak of neutrophil nasal mucosal infiltration,
suggesting a potential role of neutrophils in LXA4biosynthesis during the early phase of the allergic inflammatory
response. Last, LXA4 appeared as essential to inhibit
the in vitro release of eosinophil superoxide triggered by NK
cells.
Conclusion : Together, these findings indicate a synergistic
role for NK cells and LXA4 in the resolution of allergic
eosinophilic inflammation.