title: P-selectin glycoprotein ligand-1 regulates adhesive properties of the endothelium and leukocyte trafficking into adipose tissue.
abstract: BACKGROUND
  Adhesive interactions between endothelial cells and leukocytes affect leukocyte trafficking in adipose tissue. The role of P-selectin glycoprotein ligand-1 (Psgl-1) in this process is unclear.
  
  
  OBJECTIVE
  The goal of this study was to determine the effect of Psgl-1 deficiency on adhesive properties of the endothelium and on leukocyte recruitment into obese adipose depots.
  
  
  RESULTS
  A genetic model of obesity was generated to study the effects of Psgl-1 deficiency on leukocyte trafficking. Leukocyte-endothelial interactions were increased in obese leptin receptor mutant mice (Lepr(db/db),Psgl-1(+/+)) but not obese Psgl-1-deficient mice (Lepr(db/db),Psgl-1(-/-)), when compared with lean mice (Lepr(+/+),Psgl-1(+/+)). This effect of Psgl-1 deficiency was due to indirect effects of Psgl-1, because Psgl-1(+/+) adoptively transferred leukocytes did not exhibit enhanced rolling in Lepr (db/db),Psgl-1(-/-) mice. Additionally, circulating levels of P-selectin, E-selectin, monocyte chemoattractant protein-1, and macrophage content of visceral adipose tissue were reduced in Lepr(db/db),Psgl-1(-/-) compared with Lepr(db/db),Psgl-1(+/+) mice. Reduced leukocyte-endothelial interactions and macrophage content of visceral adipose tissue due to Psgl-1 deficiency was also observed in a diet-induced obese mouse model. Psgl-1(-/-) mice were resistant to the endothelial effects of exogenous IL-1beta, suggesting that defective cytokine signaling contributes to the effect of Psgl-1 deficiency on leukocyte-endothelial interactions. Mice deficient in the IL-1 receptor also had reduced levels of circulating P-selectin, similar to those observed in Psgl-1(-/-) mice.
  
  
  CONCLUSIONS
  Deficiency of Psgl-1 is associated with reduced IL-1 receptor-mediated adhesive properties of the endothelium and is protective against visceral fat inflammation in obese mice.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, 48109-0644, USA.
authors.forename: Hana M
authors.initials: HM
authors.lastname: Russo
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wickenheiser
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Miina K
authors.initials: MK
authors.lastname: Ohman
authors.forename: Luigi
authors.initials: L
authors.lastname: Franchi
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Wright
authors.forename: Peter F
authors.initials: PF
authors.lastname: Bodary
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Núñez
authors.initials: N
authors.lastname: Gabriel
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000821:Animal Feed; D000818:Animals; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000097:blood; D003433:Crosses, Genetic; D019040:E-Selectin / Q000097:blood; D004727:Endothelium / Q000502:physiology*; D005260:Female; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics*; D019007:P-Selectin / Q000097:blood / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D054411:Receptors, Leptin / Q000172:deficiency; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D017472:Receptors, Interleukin-1; D054411:Receptors, Leptin; C515447:leptin receptor, mouse