title: Generation of soluble P- and E-selectins in vivo is dependent on expression of P-selectin glycoprotein ligand-1.
abstract: BACKGROUND
  Factors contributing to the generation of soluble P- and E-selectins remain unclear.
  
  
  RESULTS
  This work demonstrates that mice lacking P-selectin glycoprotein ligand-1 (Psgl-1(-/-)) are deficient in soluble P-selectin (sP-sel), which is due to a defective binding interaction between PSGL-1 and P-sel, because mice lacking alpha(1,3)-fucosyltransferase-VII are also deficient in sP-sel. Psgl-1(-/-) mice are also deficient in soluble E-selectin (sE-sel) indicating that leukocyte interactions with endothelial cells lead to the generation of sE-sel. The generation of sE-sel requires an interaction between PSGL-1 and P-sel, as deficiency of sE-sel is observed in both Psgl-1(-/-) and P-sel(-/-) mice. Bone marrow transplantation from Psgl-1(-/-) to Psgl-1(+/+) mice leads to deficiency of sP-sel and sE-sel in recipient mice, establishing the importance of bone marrow-derived PSGL-1 toward the generation of sP-sel and sE-sel. Bone marrow transplantation from P-sel(-/-) to P-sel1(+/+) mice does not lead to a significant reduction in sP-sel, confirming the importance of the endothelium toward the liberation of sP-sel.
  
  
  CONCLUSIONS
  sP-sel and sE-sel reflect an interaction between leukocyte PSGL-1 and endothelial P-sel.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Bodary
authors.forename: J W
authors.initials: JW
authors.lastname: Homeister
authors.forename: F B
authors.initials: FB
authors.lastname: Vargas
authors.forename: K J
authors.initials: KJ
authors.lastname: Wickenheiser
authors.forename: S S
authors.initials: SS
authors.lastname: Cudney
authors.forename: K L
authors.initials: KL
authors.lastname: Bahrou
authors.forename: M
authors.initials: M
authors.lastname: Ohman
authors.forename: A B
authors.initials: AB
authors.lastname: Rabbani
authors.forename: D T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D019040:E-Selectin / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D005647:Fucosyltransferases / Q000172:deficiency / Q000235:genetics; D015870:Gene Expression; D005838:Genotype; D007962:Leukocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000096:biosynthesis*; D011485:Protein Binding
chemical_list: D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D005647:Fucosyltransferases; C514210:fucosyltransferase VII, mouse