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Mast cells mediate early neutrophil recruitment and exhibit anti-inflammatory
properties via the formyl peptide receptor 2/lipoxin A(4) receptor
#MMPMID28471519
Hughes EL
; Becker F
; Flower RJ
; Buckingham JC
; Gavins FNE
Br J Pharmacol
2017[Jul]; 174
(14
): 2393-2408
PMID28471519
show ga
BACKGROUND AND PURPOSE: In recent years, studies have focused on the resolution
of inflammation, which can be achieved by endogenous anti-inflammatory agonists
such as Annexin A1 (AnxA1). Here, we investigated the effects of mast cells (MCs)
on early LPS-induced neutrophil recruitment and the involvement of the
AnxA1-formyl peptide receptor 2/ALX (FPR2/ALX or lipoxin A(4) receptor) pathway.
EXPERIMENTAL APPROACH: Intravital microscopy (IVM) was used to visualize and
quantify the effects of LPS (10 ?g per mouse i.p.) on murine mesenteric cellular
interactions. Furthermore, the role that MCs play in these inflammatory responses
was determined in vivo and in vitro, and effects of AnxA1 mimetic peptide Ac2-26
were assessed. KEY RESULTS: LPS increased both neutrophil endothelial cell
interactions within the mesenteric microcirculation and MC activation (determined
by IVM and ruthenium red dye uptake), which in turn lead to the early stages of
neutrophil recruitment. MC recruitment of neutrophils could be blocked by
preventing the pro-inflammatory activation (using cromolyn sodium) or enhancing
an anti-inflammatory phenotype (using Ac2-26) in MCs. Furthermore, MCs induced
neutrophil migration in vitro, and MC stabilization enhanced the release of AnxA1
from neutrophils. Pharmacological approaches (such as the administration of FPR
pan-antagonist Boc2, or the FPR2/ALX antagonist WRW4) revealed neutrophil
FPR2/ALX to be important in this process. CONCLUSIONS AND IMPLICATIONS: Data
presented here provide evidence for a role of MCs, which are ideally positioned
in close proximity to the vasculature, to act as sentinel cells in neutrophil
extravasation and resolution of inflammation via the AnxA1-FPR2/ALX pathway.
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