Generation of soluble P- and E-selectins in vivo is dependent on expression of P-selectin glycoprotein ligand-1.
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.
Bodary
P F
PF
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Homeister
J W
JW
Vargas
F B
FB
Wickenheiser
K J
KJ
Cudney
S S
SS
Bahrou
K L
KL
Ohman
M
M
Rabbani
A B
AB
Eitzman
D T
DT
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
D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D005647:Fucosyltransferases; C514210:fucosyltransferase VII, mouse