Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse

FASEB J. 2003 Feb;17(2):253-5. doi: 10.1096/fj.02-0239fje. Epub 2002 Dec 3.


The 37-kDa protein annexin 1 (Anx-1; lipocortin 1) has been implicated in the regulation of phagocytosis, cell signaling, and proliferation and is postulated to be a mediator of glucocorticoid action in inflammation and in the control of anterior pituitary hormone release. Here, we report that mice lacking the Anx-1 gene exhibit a complex phenotype that includes an altered expression of other annexins as well as of COX-2 and cPLA2. In carrageenin- or zymosan-induced inflammation, Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. Anx-1-/- polymorphonuclear leucocytes exhibited increased spontaneous migratory behavior in vivo whereas in vitro, leukocytes from Anx-1-/- mice had reduced cell surface CD 11b (MAC-1) but enhanced CD62L (L-selectin) expression and Anx-1-/- macrophages exhibited anomalies in phagocytosis. There are also gender differences in activated leukocyte behavior in the Anx-1-/- mice that are not seen in the wild-type animals, suggesting an interaction between sex hormones and inflammation in Anx-1-/- animals.

MeSH terms

  • Animals
  • Annexin A1 / genetics*
  • Annexin A1 / metabolism
  • Carrageenan
  • Cell Adhesion Molecules / drug effects
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / drug effects
  • Cyclooxygenase 2
  • Dexamethasone / pharmacology*
  • Drug Resistance
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / genetics
  • Female
  • Genotype
  • Glucocorticoids / pharmacology*
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Interleukin-1 / metabolism
  • Isoenzymes / drug effects
  • Isoenzymes / metabolism
  • Leukocytes / cytology
  • Male
  • Mice
  • Mice, Knockout
  • Phospholipases A / drug effects
  • Phospholipases A / metabolism
  • Prostaglandin-Endoperoxide Synthases / drug effects
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Sex Factors


  • Annexin A1
  • Cell Adhesion Molecules
  • Glucocorticoids
  • Interleukin-1
  • Isoenzymes
  • Dexamethasone
  • Carrageenan
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Phospholipases A