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

Robert Hannon*, Jamie D. Croxtall, Steve J. Getting, Fiorita Roviezzo, Simon Yona, Mark J. Paul-Clark, Felicity N.E. Gavins, Mauro Perretti, John F. Morris, Julia C. Buckingham, Roderick J. Flower

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

312 Scopus citations

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-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.

Original languageAmerican English
Pages (from-to)253-255
Number of pages3
JournalFASEB Journal
Volume17
Issue number2
DOIs
StatePublished - Feb 2003
Externally publishedYes

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