The role of the Annexin-A1/FPR2 system in the regulation of mast cell degranulation provoked by compound 48/80 and in the inhibitory action of nedocromil

International Immunopharmacology
Ajantha SinniahR J Flower

Abstract

1.We investigated the role of Annexin (ANX)-A1 and its receptor, ALX/FPR2, in the regulation of mast cell degranulation produced by compound 48/80. 2.Both human cord-blood derived mast cells (CBDMCs) and murine bone marrow derived mast cells (BMDMCs) release phosphorylated ANX-A1 during treatment with glucocorticoids or the mast cell 'stabilising' drugs ketotifen and nedocromil. 3.Compound 48/80 also stimulated ANX-A1 phosphorylation and release and this was also potentiated by nedocromil. Anti-ANX-A1 neutralising monoclonal antibodies (Mabs) enhanced the release of pro-inflammatory mediators in response to compound 48/80. 4.Nedocromil and ketotifen potently inhibited the release of histamine, PGD2, tryptase and β-hexosaminidase from mast cells challenged with compound 48/80. Anti-ANX-A1 neutralising Mabs prevented the inhibitory effect of these drugs. 5.BMDMCs derived from Anx-A1−/− mice were insensitive to the inhibitory effects of nedocromil or ketotifen but cells retained their sensitivity to the inhibitory action of hu-r-ANX-A1. 6.The fpr2/3 antagonist WRW4 blocked the action of nedocromil on PGD2, but not histamine, release. BMDMCs derived from fpr2/3−/− mice were insensitive to the inhibitory effects of nedocromil on PGD...Continue Reading

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Citations

Dec 1, 2017·Frontiers in Pharmacology·Ajantha SinniahRoderick J Flower
May 28, 2016·Biological Chemistry·Giovanna Leoni, Asma Nusrat
Jul 23, 2016·Biological Chemistry·Thomas Gobbetti, Sadani N Cooray
Dec 5, 2019·Frontiers in Pharmacology·Ajantha SinniahRod J Flower
Mar 17, 2018·Journal of Translational Medicine·Yung-Che ChenUNKNOWN Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group
May 4, 2020·The Ocular Surface·Becca A FlitterKarsten Gronert
Apr 4, 2021·International Journal of Molecular Sciences·Thomas GrewalUrsula Rescher

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