The annexin-1 knockout mouse: what it tells us about the inflammatory response.
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.
Roviezzo
F
F
Department of Biochemical Pharmacology, William Harvey Research Institute, Queen Mary, University of London, UK.
Getting
S J
SJ
Paul-Clark
M J
MJ
Yona
S
S
Gavins
F N E
FN
Perretti
M
M
Hannon
R
R
Croxtall
J D
JD
Buckingham
J C
JC
Flower
R J
RJ
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
D017305:Annexin A1