Aberrant inflammation and resistance to glucocorticoids in Annexin 1-/- Mouse

被引:304
作者
Hannon, R
Croxtall, JD
Getting, SJ
Roviezzo, F
Yona, S
Paul-Clark, MJ
Gavins, FNE
Perretti, M
Morris, JF
Buckingham, JC
Flower, RJ
机构
[1] Univ London, Queen Mary, William Harvey Res Inst, Dept Biochem Pharmacol, London EC1M 6BQ, England
[2] Univ Naples Federico II, Dipartimento Farmacol Sperimentale Federico II, Naples, Italy
[3] Univ Oxford, Dept Human Anat & Genet, Oxford OX1 3QX, England
[4] Imperial Coll Sch Med, Div Neurosci & Psychol Med, London W12 0NN, England
关键词
neutrophil activation; cell adhesion molecules; phagocytosis; cytokines; edema;
D O I
10.1096/fj.02-0239fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-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.
引用
收藏
页码:253 / +
页数:22
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