Mast cells mediate early neutrophil recruitment and exhibit anti-inflammatory properties via the formyl peptide receptor 2/lipoxin A 4 receptor.

Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE

Publication: London : Wiley
Original Publication: London, Macmillian Journals Ltd.

Anti-Inflammatory Agents/*pharmacology ; Mast Cells/*drug effects ; Mast Cells/*metabolism ; Neutrophil Infiltration/*drug effects ; Receptors, Formyl Peptide/*metabolism; Animals ; Annexin A1/chemistry ; Annexin A1/pharmacology ; Anti-Inflammatory Agents/chemistry ; Cromolyn Sodium/chemistry ; Cromolyn Sodium/pharmacology ; Endothelial Cells/drug effects ; Intravital Microscopy ; Lipopolysaccharides/chemistry ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Neutrophils/drug effects ; Peptides/chemistry ; Peptides/pharmacology

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 μg 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.
(© 2017 The British Pharmacological Society.)

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MC_PC_12015 United Kingdom MRC_ Medical Research Council

0 (Annexin A1)
0 (Anti-Inflammatory Agents)
0 (Fpr1 protein, mouse)
0 (Lipopolysaccharides)
0 (Peptides)
0 (Receptors, Formyl Peptide)
0 (annexin A1 peptide (2-26))
0 (formyl peptide receptor 2, mouse)
Q2WXR1I0PK (Cromolyn Sodium)

Date Created: 20170505 Date Completed: 20180216 Latest Revision: 20220129

20231215

PMC5481652

10.1111/bph.13847

28471519