title: Intercellular adhesion molecule-1 blockade attenuates inflammatory response and improves microvascular perfusion in rat pancreas grafts.
abstract: OBJECTIVE
  After pancreas transplantation (PTx), early capillary malperfusion and leukocyte recruitment indicate the manifestation of severe ischemia/reperfusion injury (IRI). Oscillatory blood-flow redistribution (intermittent capillary perfusion, IP), leading to an overall decrease in erythrocyte flux, precedes complete microvascular perfusion failure with persistent blood flow cessation. We addressed the role of intercellular adhesion molecule-1 (ICAM-1) for leukocyte-endothelial interactions (LEIs) after PTx and evaluated the contribution of IP and malperfusion.
  
  
  METHODS
  Pancreas transplantation was performed in rats after 18-hour preservation, receiving either isotype-matched IgG or monoclonal anti-ICAM-1 antibodies (10 mg/kg intravenously) once before reperfusion. Leukocyte-endothelial interaction, IP, erythrocyte flux, and functional capillary density, respectively, were examined in vivo during 2-hour reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry.
  
  
  RESULTS
  In grafts of IgG-treated animals, IP was encountered already at an early stage after reperfusion and steadily increased over 2 hours, whereas erythrocyte flux declined continuously. In contrast, inhibition of ICAM-1 significantly improved erythrocyte flux and delayed IP appearance by 2 hours. Further, anti-ICAM-1 significantly reduced LEI and leukocyte tissue infiltration when compared to IgG; edema development was less pronounced in response to anti-ICAM-1 monoclonal antibody.
  
  
  CONCLUSIONS
  Intercellular adhesion molecule-1 blockade significantly attenuates IRI via immediate reduction of LEI and concomitant improvement of capillary perfusion patterns, emphasizing its central role during IRI in PTx.
authors.affiliation: Department of Surgery, Institute for Surgical Research, Walter-Brendel-Centre for Experimental Medicine, Ludwig-Maximilians-University of Munich, Campus Grosshadern, Munich, Germany. gerhard.preissler@med.uni-muenchen.de
authors.forename: Gerhard
authors.initials: G
authors.lastname: Preissler
authors.forename: Martin
authors.initials: M
authors.lastname: Eichhorn
authors.forename: Helmut
authors.initials: H
authors.lastname: Waldner
authors.forename: Hauke
authors.initials: H
authors.lastname: Winter
authors.forename: Axel
authors.initials: A
authors.lastname: Kleespies
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002196:Capillaries / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology; D007249:Inflammation / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D010179:Pancreas / Q000098:blood supply* / Q000473:pathology; D016035:Pancreas Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1