Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 12, Pages 3436-3442Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201141764
Keywords
ADAM8; Adhesion; Cell migration; ERM; Neutrophil; PSGL-1
Categories
Funding
- Ministry of Health (Fondo de Investigaciones Sanitarias) [FIS-PI080894, FIS 09/02209]
- Ministerio de Ciencia e Innovacion [SAF2008-02635, SAF2008-02251]
- Redes RIER, RTICC [RD06/0020/1037]
- RECAVA del Instituto de Salud Carlos III
- RTICCR
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The P-selectin glycoprotein ligand-1 ( PSGL-1) is involved in the initial contact of leukocytes with activated endothelium, and its adhesive function is regulated through its proteolytic processing. We have found that the metalloprotease ADAM8 is both associated with PSGL-1 through the ezrin-radixin-moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor. Accordingly, ADAM8 knockdown increases PSGL-1 expression, and functional assays show that ADAM8 is able to reduce leukocyte rolling on P-selectin and hence on activated endothelial cells. We conclude that ADAM8 modulates the expression and function of PSGL-1.
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