title: Direct in vivo observations of P-selectin glycoprotein ligand-1-mediated leukocyte-endothelial cell interactions in the pulmonary microvasculature in abdominal sepsis in mice.
abstract: OBJECTIVE
  P-selectin glycoprotein ligand-1 (PSGL-1) has been shown to play a significant role in septic lung injury. However, the detailed role of PSGL-1 in the pulmonary leukocyte recruitment remains elusive. We have developed a method based on intravital fluorescence microscopy of the lung microcirculation to examine the role of PSGL-1 in the extravasation process of leukocytes in septic lung damage.
  
  
  METHODS
  Male C57BL/6 mice were treated with a control antibody or an anti-PSGL-1 antibody prior to cecal ligation and puncture (CLP). Leukocyte-endothelium interactions and microvascular hemodynamics were studied in pulmonary arterioles, capillaries and venules 4 h after CLP.
  
  
  RESULTS
  Immunoneutralization of PSGL-1 decreased CLP-induced leukocyte rolling in pulmonary arterioles and venules significantly. Inhibition of PSGL-1 had no effect on leukocyte adhesion in venules, whereas the number of adherent leukocytes in lung arterioles and the number of trapped leukocytes in capillaries were markedly decreased. Moreover, immunoneutralization of PSGL-1 improved microvascular perfusion in the lung of septic animals.
  
  
  CONCLUSIONS
  Taken together, these results document that PSGL-1 mediates leukocyte rolling in arterioles and venules. However, inhibition of PSGL-1 only decreases leukocyte adhesion in arterioles, suggesting that leukocyte rolling is not a prerequisite for pulmonary venular adhesion of leukocytes in sepsis. In addition, our data show that capillary trapping of leukocytes is dependent on PSGL-1 function.
authors.affiliation: Department of Clinical Sciences, Section of Surgery, Lund University, 20502 Malmö, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Roller
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Rahman
authors.forename: R
authors.initials: R
authors.lastname: Schramm
authors.forename: M W
authors.initials: MW
authors.lastname: Laschke
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
authors.forename: B
authors.initials: B
authors.lastname: Jeppsson
authors.forename: H
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000005:Abdomen / Q000382:microbiology; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000502:physiology; D007962:Leukocytes / Q000473:pathology / Q000502:physiology*; D008168:Lung / Q000098:blood supply* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D055806:Microvessels / Q000503:physiopathology*; D018805:Sepsis / Q000382:microbiology / Q000503:physiopathology*
chemical_list: D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein