title: The annexin-1 knockout mouse: what it tells us about the inflammatory response.
abstract: The 37kDa protein annexin 1 (Anx-1; lipocortin 1) is a glucocorticoid-regulated protein that has been implicated in the regulation of phagocytosis, cell signalling and proliferation, and postulated to be a mediator of glucocorticoids action in inflammation and in the control of anterior pituitary hormone release. Immuno-neutralisation or antisense strategies support this hypothesis as they can reverse the effect of glucocorticoids in several systems. We recently generated a line of mice lacking the Anx-1 gene noting that some tissues taken from such animals exhibited an increased expression of several proteins including COX-2 and cPLA2. In models of experimental inflammation, Anx-1(-/-) mice exhibit an exaggerated response and a partial or complete resistance to the anti-inflammatory effects of glucocorticoids. Several other anomalies were noted including abnormal leukocyte adhesion molecule expression, an increased spontaneous migratory behaviour of PMN in Anx-1(-/-) mice and a resistance in Anx-1(-/-) macrophages to glucocorticoid inhibition of superoxide generation. This paper reviews these and other data in the light of the development of the 'second messenger' hypothesis of glucocorticoid action.
authors.affiliation: Department of Biochemical Pharmacology, William Harvey Research Institute, Queen Mary, University of London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Roviezzo
authors.forename: S J
authors.initials: SJ
authors.lastname: Getting
authors.forename: M J
authors.initials: MJ
authors.lastname: Paul-Clark
authors.forename: S
authors.initials: S
authors.lastname: Yona
authors.forename: F N E
authors.initials: FN
authors.lastname: Gavins
authors.forename: M
authors.initials: M
authors.lastname: Perretti
authors.forename: R
authors.initials: R
authors.lastname: Hannon
authors.forename: J D
authors.initials: JD
authors.lastname: Croxtall
authors.forename: J C
authors.initials: JC
authors.lastname: Buckingham
authors.forename: R J
authors.initials: RJ
authors.lastname: Flower
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015290:Second Messenger Systems / Q000502:physiology
chemical_list: D017305:Annexin A1