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- Title
Aberrant inflammation and resistance to glucocorticoids in Annexin 1<sup>−/−</sup> Mouse.
- Authors
Hannon, Robert; Croxtall, Jamie D.; Getting, Stephen J.; Roviezzo, Fiorentina; Yona, Simon; Paul‐Clark, Mark J.; Gavins, Felicity N. E.; Perretti, Mauro; Morris, John F.; Buckingham, Julia C.; Flower, Roderick J.
- Abstract
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‐1β 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.
- Publication
FASEB Journal, 2003, Vol 17, Issue 2, p253
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.02-0239fje