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Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling.
- Source :
-
Circulation research [Circ Res] 2009 Sep 25; Vol. 105 (7), pp. 696-704, 8 p following 704. Date of Electronic Publication: 2009 Aug 20. - Publication Year :
- 2009
-
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).<br />Objective: We investigated the role of BMPCs in annealing AJs and thereby in preventing lung edema formation induced by endotoxin (LPS).<br />Methods and Results: 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.<br />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.
- Subjects :
- Animals
Bone Marrow Transplantation
Cell Movement
Cell Separation
Cells, Cultured
Coculture Techniques
Disease Models, Animal
Endothelial Cells pathology
Enzyme Activation
Flow Cytometry
Humans
Lipopolysaccharides
Lung blood supply
Lung pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Paracrine Communication
Phosphotransferases (Alcohol Group Acceptor) deficiency
Phosphotransferases (Alcohol Group Acceptor) genetics
Pulmonary Edema chemically induced
Pulmonary Edema pathology
Pulmonary Edema prevention & control
Signal Transduction
Sphingosine metabolism
Time Factors
rac1 GTP-Binding Protein
Adherens Junctions enzymology
Bone Marrow Cells enzymology
Capillary Permeability
Endothelial Cells enzymology
Lung enzymology
Lysophospholipids metabolism
Neuropeptides metabolism
Pulmonary Edema enzymology
Sphingosine analogs & derivatives
Stem Cells enzymology
cdc42 GTP-Binding Protein metabolism
rac GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 105
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 19696411
- Full Text :
- https://doi.org/10.1161/CIRCRESAHA.109.199778