The annexin-1 knockout mouse: What it tells us about the inflammatory response

F. Roviezzo, S. J. Getting, M. J. Paul-Clark, S. Yona, F. N.E. Gavins, M. Perretti, R. Hannon, J. D. Croxtall, J. C. Buckingham, R. J. Flower*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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.

Original languageAmerican English
Pages (from-to)541-553
Number of pages13
JournalJournal of Physiology and Pharmacology
Volume53
Issue number4 I
StatePublished - Dec 2002
Externally publishedYes

Keywords

  • Annexins
  • Glucocorticoids
  • Inflammation
  • Transgenic animal models

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