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Resolving inflammation in stroke through FPR2/ALX
Author(s) -
smith helen k,
gavins felicity
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.678.11
Subject(s) - inflammation , annexin a1 , pharmacophore , lipoxin , stroke (engine) , formyl peptide receptor , ischemia , pharmacology , intravital microscopy , receptor , annexin , brain ischemia , chemistry , medicine , microcirculation , chemotaxis , biochemistry , in vitro , mechanical engineering , engineering
Ischaemia/reperfusion (I/R) injury in stroke can worsen patient outcome through excess inflammation. We investigated the pharmacological potential of an endogenous anti‐inflammatory mechanism, formyl peptide receptor 2/lipoxin receptor (FPR2/ALX; Fpr2/Fpr3 in mouse), in reducing I/R‐associated inflammation in a mouse model of stroke. Mice underwent 5 min global cerebral ischaemia, followed by 40 min or 2 h reperfusion. FPR agonists—Ac2‐26 (Annexin A1 pharmacophore) and 15‐epi‐lipoxin A4—were administered at the start of reperfusion. Subsequent leukocyte‐endothelial (L‐E) interactions (characteristic of an inflammatory response) were quantified through a cranial window using intravital video microscopy. 15‐epi‐lipoxin A4 administration dramatically reduced L‐E interactions at 40 min reperfusion but less so at 2 h. Ac2‐26 treatment decreased leukocyte adhesion at 40 min and all L‐E interactions at 2 h. Combined treatment with Ac2‐26 plus FPR antagonists Boc2 or WRW4 (FPR2/ALX‐selective) abrogated the effects of Ac2‐26. We show that activity through Fpr2/Fpr3 reduces L‐E interactions in a model of global cerebral I/R. These data provide evidence that FPR2/ALX could be a therapeutic target in stroke. This was funded by the BBSRC.