E-selectin binding promotes neutrophil activation in vivo in E-selectin transgenic mice.
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.
Araki
M
M
Department of Pathology, Centre Médical Universitaire, University of Geneva, Switzerland.
Araki
K
K
Miyazaki
Y
Y
Iwamoto
M
M
Izui
S
S
Yamamura
K
K
Vassalli
P
P
D000199:Actins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D005453:Fluorescence; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics
D000199:Actins; D019040:E-Selectin; D012333:RNA, Messenger