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Aberrant inflammation and resistance to glucocorticoids in Annexin 1 −/− Mouse
Author(s) -
Han Robert,
Croxtall Jamie D.,
Getting Stephen J.,
Roviezzo Fiorentina,
Yona Simon,
PaulClark Mark J.,
Gavins Felicity N. E.,
Perretti Mauro,
Morris John F.,
Buckingham Julia C.,
Flower Roderick J.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0239fje
Subject(s) - inflammation , annexin a1 , phagocytosis , endocrinology , annexin , zymosan , medicine , glucocorticoid , biology , macrophage , microbiology and biotechnology , immunology , in vitro , flow cytometry , biochemistry
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 cPLA 2 . 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.