Complete downmodulation of P-selectin glycoprotein ligand in monocytes undergoing apoptosis.
Arterioscler Thromb Vasc Biol
; 28(7): 1375-8, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18451333
ABSTRACT
OBJECTIVE:
Apoptotic monocytes release membrane microparticles which may play a major role in thrombogenicity through a P-selectin glycoprotein ligand (PGSL-1)-mediated mechanism. We have studied systematically the regulation of PSGL-1 expression and function in apoptotic monocytic cells. METHODS ANDRESULTS:
PSGL-1 expression (flow cytometry, immunofluorescence microscopy, immunoblot) was virtually abolished in apoptotic monocytes by proteolytic shedding. This was accompanied by a complete loss of PSGL-1-mediated platelet-leukocyte (flow cytometry) and leukocyte-endothelial cell (parallel plate flow chamber) interactions. Systematic screening of protease inhibitors combined with knock-out and siRNA experiments characterized the PSGL-1-cleaving enzyme as an N-ethylmaleimide-inhibitable metalloproteinase of the ADAM family.CONCLUSIONS:
Downmodulation of PGSL-1 in apoptotic monocytes may prevent ectopic cell clearance in the peripheral vasculature to reduce local inflammatory and proliferative responses. Depletion of PSGL-1 expression on apoptotic microparticles may also act as a molecular switch to modulate their thrombogenic activity.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
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Monocitos
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Apoptosis
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Vesículas Transportadoras
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Proteínas ADAM
Límite:
Animals
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Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania