title: Inhibition of lectin-like oxidized low-density lipoprotein receptor-1 reduces leukocyte adhesion within the intestinal microcirculation in experimental endotoxemia in rats.
abstract: BACKGROUND
  Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the major endothelial receptor for oxidized low-density lipoprotein, is also involved in leukocyte recruitment. Systemic leukocyte activation in sepsis represents a crucial factor in the impairment of the microcirculation of different tissues, causing multiple organ failure and subsequently death. The aim of our experimental study was to evaluate the effects of LOX-1 inhibition on the endotoxin-induced leukocyte adherence and capillary perfusion within the intestinal microcirculation by using intravital microscopy (IVM).
  
  
  METHODS
  We used 40 male Lewis rats for the experiments. Ten placebo-treated animals served as a control. Thirty animals received 5 mg/kg lipopolysaccharide (LPS) intravenously. Ten endotoxemic rats remained untreated. In 10 LPS animals, we administered additionally 10 mg/kg LOX-1 antibodies. Ten further LPS animals received a nonspecific immunoglobulin (rat IgG) intravenously. After 2 hours of observation, intestinal microcirculation was evaluated by using IVM; the plasma levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) were determined; and LOX-1 expression was quantified in intestinal tissue with Western blot and reverse-transcription polymerase chain reaction (PCR).
  
  
  RESULTS
  LOX-1 inhibition significantly reduced LPS-induced leukocyte adhesion in intestinal submucosal venules (P < 0.05). At the protein and mRNA levels, LOX-1 expression was significantly increased in untreated LPS animals (P < 0.05), whereas in animals treated with LOX-1 antibody, expression of LOX-1 was reduced (P < 0.05). MCP-1 plasma level was reduced after LOX-1 antibody administration.
  
  
  CONCLUSIONS
  Inhibition of LOX-1 reduced leukocyte activation in experimental endotoxemia. LOX-1 represents a novel target for the modulation of the inflammatory response within the microcirculation in sepsis.
authors.affiliation: Department of Internal Medicine B, University Hospital Greifswald, Friedrich-Loeffler-Strasse 23 a, D-17475 Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Landsberger
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wilk
authors.forename: Corinna
authors.initials: C
authors.lastname: Thaumüller
authors.forename: Dragan
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Marion
authors.initials: M
authors.lastname: Otto
authors.forename: Sara
authors.initials: S
authors.lastname: Whynot
authors.forename: Orlando
authors.initials: O
authors.lastname: Hung
authors.forename: Michael F
authors.initials: MF
authors.lastname: Murphy
authors.forename: Vladimir
authors.initials: V
authors.lastname: Cerny
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000276:immunology; D019446:Endotoxemia / Q000276:immunology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000276:immunology / Q000473:pathology*; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D051127:Scavenger Receptors, Class E