Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling.
Circ Res
; 105(7): 696-704, 8 p following 704, 2009 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-19696411
ABSTRACT
RATIONALE Little is known about the contribution of bone marrow-derived progenitor cells (BMPCs) in the regulation endothelial barrier function as defined by microvascular permeability alterations at the level of adherens junctions (AJs). OBJECTIVE:
We investigated the role of BMPCs in annealing AJs and thereby in preventing lung edema formation induced by endotoxin (LPS). METHODS ANDRESULTS:
We observed that BMPCs enhanced basal endothelial barrier function and prevented the increase in pulmonary microvascular permeability and edema formation in mice after LPS challenge. Coculture of BMPCs with endothelial cells induced Rac1 and Cdc42 activation and AJ assembly in endothelial cells. However, transplantation of BMPCs isolated from sphingosine kinase-1-null mice (SPHK1(-/-)), having impaired S1P production, failed to activate Rac1 and Cdc42 or protect the endothelial barrier.CONCLUSIONS:
These results demonstrate that BMPCs have the ability to reanneal endothelial AJs by paracrine S1P release in the inflammatory milieu and the consequent activation of Rac-1 and Cdc42 in endothelial cells.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Edema Pulmonar
/
Esfingosina
/
Células Madre
/
Neuropéptidos
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Permeabilidad Capilar
/
Células de la Médula Ósea
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Lisofosfolípidos
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Proteína de Unión al GTP cdc42
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Proteínas de Unión al GTP rac
/
Uniones Adherentes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Circ Res
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos