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Proc Natl Acad Sci U S A ; 103(34): 12825-30, 2006 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-16908865

RESUMEN

Deletion of apoptotic cells from tissues involves their phagocytosis by macrophages, dendritic cells, and tissue cells. Although much attention has been focused on the participating ligands, receptors, and mechanisms of uptake, little is known of the disposition of the ingested cell within the phagosome. Here we show that uptake of apoptotic cells by macrophages or fibroblasts results in rapid phagosome maturation, whereas macrophage phagosomes containing Ig-opsonized target cells mature at a slower rate. The early maturation was shown to depend on activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins. Blockade of Rho signaling or inhibition of moesin both delayed maturation rates to those seen with opsonized targets. By contrast, phagosome maturation in dendritic cells was slower, similar between apoptotic and opsonized target cells, and unaffected by Rho inhibition. These observations have direct implications for the clearance of dying cells and the roles played by different phagocytes in antigen digestion and presentation.


Asunto(s)
Proteínas del Citoesqueleto/metabolismo , Células Dendríticas/citología , Células Dendríticas/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Fagosomas/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Ácidos , Animales , Apoptosis , Línea Celular , Células Dendríticas/enzimología , Humanos , Concentración de Iones de Hidrógeno , Macrófagos/enzimología , Proteínas de la Membrana/metabolismo , Ratones , Proteínas de Microfilamentos/metabolismo , Transducción de Señal
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