title: Bone marrow progenitor cells induce endothelial adherens junction integrity by sphingosine-1-phosphate-mediated Rac1 and Cdc42 signaling.
abstract: 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.
authors.affiliation: Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Ill. 60612, USA. yidanzhao@gmail.com
authors.forename: Yidan D
authors.initials: YD
authors.lastname: Zhao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohkawara
authors.forename: Jalees
authors.initials: J
authors.lastname: Rehman
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Wary
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Vogel
authors.forename: Richard D
authors.initials: RD
authors.lastname: Minshall
authors.forename: You-Yang
authors.initials: YY
authors.lastname: Zhao
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
mesh_terms: 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
chemical_list: 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
references.citation: Anal Biochem. 2005 Apr 1;339(1):129-36
references.pmid: 15766719
references.citation: J Biol Chem. 2005 Apr 29;280(17):17320-8
references.pmid: 15728185
references.citation: Cell. 1999 Oct 29;99(3):301-12
references.pmid: 10555146
references.citation: Am J Respir Crit Care Med. 2004 Jun 1;169(11):1245-51
references.pmid: 15020292
references.citation: J Biol Chem. 2004 Dec 10;279(50):52487-92
references.pmid: 15459201
references.citation: Circ Res. 2008 Mar 28;102(6):669-76
references.pmid: 18258856
references.citation: Pharmacol Ther. 2000 Nov;88(2):115-31
references.pmid: 11150592
references.citation: Circ Res. 2008 Jul 18;103(2):203-11
references.pmid: 18566343
references.citation: Blood. 2007 Mar 1;109(5):1801-9
references.pmid: 17053059
references.citation: Circ Res. 1988 Oct;63(4):735-41
references.pmid: 3168176
references.citation: PLoS Med. 2007 Sep;4(9):e269
references.pmid: 17803352
references.citation: J Biol Chem. 2003 Aug 29;278(35):33492-500
references.pmid: 12766172
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1981 Jan;50(1):102-6
references.pmid: 7204179
references.citation: J Biol Chem. 1997 Oct 10;272(41):25968-75
references.pmid: 9325331
references.citation: Science. 2007 Apr 13;316(5822):295-8
references.pmid: 17363629
references.citation: J Biol Chem. 2001 Jun 22;276(25):22614-20
references.pmid: 11309397
references.citation: Transl Res. 2008 Nov;152(5):213-24
references.pmid: 19010292
references.citation: J Lipid Res. 2005 Nov;46(11):2458-67
references.pmid: 16061940
references.citation: Blood. 2004 Nov 1;104(9):2752-60
references.pmid: 15226175
references.citation: FASEB J. 2007 Apr;21(4):1202-9
references.pmid: 17215483
references.citation: J Clin Invest. 2001 Sep;108(5):689-701
references.pmid: 11544274
references.citation: J Immunol. 2007 Aug 1;179(3):1855-63
references.pmid: 17641052
references.citation: J Biol Chem. 2003 May 2;278(18):16230-6
references.pmid: 12595527
references.citation: Eur Heart J. 2006 Dec;27(23):2775-83
references.pmid: 17098754
references.citation: Circ Res. 2005 Mar 4;96(4):442-50
references.pmid: 15692087
references.citation: Physiol Rev. 2006 Jan;86(1):279-367
references.pmid: 16371600
references.citation: Mol Cell Biol. 2004 Sep;24(17):7359-69
references.pmid: 15314148
references.citation: Circ Res. 2006 Jan 6;98(1):73-80
references.pmid: 16322481
references.citation: Circulation. 2003 Mar 4;107(8):1164-9
references.pmid: 12615796
references.citation: Curr Opin Chem Biol. 2003 Aug;7(4):461-8
references.pmid: 12941420