Araki M, Araki K, Miyazaki Y, Iwamoto M, Izui S, Yamamura K, Vassalli P
Department of Pathology, Centre Médical Universitaire, University of Geneva, Switzerland.
Biochem Biophys Res Commun. 1996 Jul 25;224(3):825-30. doi: 10.1006/bbrc.1996.1107.
E-selectin is a membrane protein expressed by endothelial cells activated by cytokines released during the inflammatory process; it plays an important role in neutrophil emigration into inflamed tissues. To further explore in vivo the function of E-selectin, we have generated transgenic mouse line expressing E-selectin under the control of a chicken beta-actin promoter. In these mice, the number of blood neutrophils was reduced, without any other obvious phenotype or tissue damage. These neutrophils, however, displayed two significant changes: first, an alteration in the levels of expression of two membrane receptors involved in neutrophil adhesion to endothelial cells, namely a marked increased in the Mac-1 antigen (CD11b/CD18) and a decrease in the Mel-14 antigen (L-selectin); second, an increased oxidative activity when compared to blood neutrophils of non-transgenic mice, as shown by their capacity to oxidize 2',7'-dichlorofluorescein (DCFH) into a fluorescent compound. These observations indicate that the binding of E-selection with neutrophils bearing its ligands promotes neutrophil activation in vivo.
E-选择素是一种膜蛋白，由炎症过程中释放的细胞因子激活的内皮细胞表达；它在中性粒细胞迁移到炎症组织中起重要作用。为了进一步在体内探索E-选择素的功能，我们构建了在鸡β-肌动蛋白启动子控制下表达E-选择素的转基因小鼠品系。在这些小鼠中，血液中性粒细胞数量减少，没有任何其他明显的表型或组织损伤。然而，这些中性粒细胞表现出两个显著变化：第一，参与中性粒细胞与内皮细胞黏附的两种膜受体表达水平改变，即Mac-1抗原（CD11b/CD18）显著增加，Mel-14抗原（L-选择素）减少；第二，与非转基因小鼠的血液中性粒细胞相比，氧化活性增加，这通过它们将2',7'-二氯荧光素（DCFH）氧化成荧光化合物的能力得以体现。这些观察结果表明，E-选择素与其配体结合的中性粒细胞在体内促进中性粒细胞激活。
