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 ho...

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Bibliographic Details
Published in:Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2002-12, Vol.53 (4 Pt 1), p.541-553
Main Authors: Roviezzo, F, Getting, S J, Paul-Clark, M J, Yona, S, Gavins, F N E, Perretti, M, Hannon, R, Croxtall, J D, Buckingham, J C, Flower, R J
Format: Article
Language:English
Subjects:
Animals
Annexin A1 - metabolism
Inflammation - physiopathology
Mice
Mice, Knockout
Models, Biological
Second Messenger Systems - physiology
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Summary: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.
ISSN:0867-5910