title: Analysis of the protection afforded by annexin 1 in ischaemia-reperfusion injury: focus on neutrophil recruitment.
abstract: Ischaemia-reperfusion injury underlies many of the most important cardiovascular diseases such as myocardial infarction, thrombotic stroke, embolic vascular occlusions and peripheral vascular insufficiency. Neutrophils feature prominently in this inflammatory component of post-ischaemic injury. Experimental therapies, shown to reduce neutrophil-mediated ischaemia-reperfusion injury include neutrophil depletion, direct inhibitors of neutrophil activators, antibodies against neutrophil adhesion molecules and the endothelial adhesion molecules. However, aside from these approaches, it is increasingly recognised that glucocorticoids are potent inhibitors of neutrophil-mediated injury. The anti-inflammatory actions of glucocorticoid include the activation of classical cytoplasmic receptors leading to changes in gene transcription as well as the induction of regulatory proteins, such as annexin 1. Annexin 1 is a potent inhibitor of neutrophil extravasation in vivo. Administration of the annexin 1 or peptides derived from its N-terminal domain, reduce neutrophil extravasation in models of acute inflammation. In addition, as reviewed by this article, annexin 1 protects against ischaemia-reperfusion in the heart and mesenteric microcirculation, as well as in multiple organ failure associated with splanchnic ischaemia-reperfusion. Such findings would suggest annexin 1 is a novel anti-inflammatory agent with a potential for the treatment of cardiovascular pathologies associated with neutrophil activation and recruitment.
authors.affiliation: Department of Biochemical Pharmacology, Division of Pharmacology, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK. m.la@mds.qmw.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: La
authors.forename: A
authors.initials: A
authors.lastname: Tailor
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
authors.forename: R J
authors.initials: RJ
authors.lastname: Flower
authors.forename: M
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D020556:Neutrophil Infiltration; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D017305:Annexin A1