Aberrant inflammation and resistance to glucocorticoids in Annexin 1-/- Mouse
Aberrant inflammation and resistance to glucocorticoids in Annexin 1-/- Mouse
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DOI：
10.1096/fj.02-0239fje
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发表时间：
2002-12-01
期刊：
影响因子：
4.8
通讯作者：
Flower, RJ
中科院分区：
文献类型：
--
作者：
Hannon, R;Croxtall, JD;Flower, RJ
37 kDa 蛋白膜联蛋白 1（Anx-1；脂皮质素 1）与吞噬作用、细胞信号传导和增殖的调节有关，并被认为是炎症中糖皮质激素作用和控制垂体前叶激素释放的介质。在此，我们报告缺乏 Anx-1 基因的小鼠表现出复杂的表型，其中包括其他膜联蛋白以及 COX-2 和 cPLA(2) 表达的改变。在角叉菜胶或酵母聚糖诱导的炎症中，Anx-1(-/-)小鼠表现出对刺激的过度反应，其特征是白细胞迁移和IL-1β生成增加以及对糖皮质激素的抗炎作用部分或完全抵抗。 Anx-1(-/-) 多形核白细胞在体内表现出自发迁移行为增加，而在体外，Anx-1(-/-) 小鼠的白细胞细胞表面 CD 11b (MAC-1) 减少，但 CD62L (L-选择素) 表达增强，Anx-1(-/-) 巨噬细胞在吞噬作用中表现出异常。 Anx-1(-/-) 小鼠的激活白细胞行为也存在性别差异，而这在野生型动物中未见，这表明 Anx-1(-/-) 动物中性激素与炎症之间存在相互作用。
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.