Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling.
BACKGROUND
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).


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.


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.
Zhao
Yidan D
YD
Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Ill. 60612, USA. yidanzhao@gmail.com
Ohkawara
Hiroshi
H
Rehman
Jalees
J
Wary
Kishore K
KK
Vogel
Stephen M
SM
Minshall
Richard D
RD
Zhao
You-Yang
YY
Malik
Asrar B
AB
D022005:Adherens Junctions / Q000201:enzymology*; D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology*; D016026:Bone Marrow Transplantation; D002199:Capillary Permeability; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism*; D019899:Paracrine Communication; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000235:genetics; D011654:Pulmonary Edema / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D013234:Stem Cells / Q000201:enzymology*; D013997:Time Factors; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein; D000099157:Sphingosine Kinase
D008070:Lipopolysaccharides; D008246:Lysophospholipids; D009479:Neuropeptides; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000099157:Sphingosine Kinase; C484602:Rac1 protein, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4; C060506:sphingosine 1-phosphate
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