title: Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: an in vivo study.
abstract: OBJECTIVE
  Patients with liver cirrhosis are predisposed to develop bacterial infections. An essential process in inflammatory responses is the recruitment of circulating leukocytes through the activation of adhesion molecules. Interferon-alpha2a is a cytokine reported to influence the expression of adhesion molecules. We investigated the effect of peginterferon-alpha2a (PegIFN-alpha(2a)) in vivo on the leukocyte recruitment in the mesenteric microcirculation of cirrhotic rats after lipopolysaccharide exposure.
  
  
  METHODS
  Leukocyte rolling, adhesion and extravasation were visualized by intravital microscopy in sham-operated and common bile duct ligated (CBDL) rats. PegIFN-alpha(2a) was administered to influence leukocyte recruitment. Endothelial P-selectin, E-selectin and ICAM-1 expression were studied by immunohistochemistry.
  
  
  RESULTS
  CBDL placebo rats showed significantly impaired rolling, adhesion and extravasation of leukocytes compared to Sham-operated placebo rats. Endothelial P-selectin, E-selectin and ICAM-1 expressions in CBDL placebo rats were significantly reduced compared to Sham-operated placebo rats. PegIFN-alpha(2a) 18 microg normalized number of rolling leukocytes in CBDL rats, without influencing on adhering and extravasated leukocytes. PegIFN-alpha(2a) upregulates the expression of P-selectin and E-selectin in CBDL rats, but ICAM-1 expression remained significantly lower than in Sham rats.
  
  
  CONCLUSIONS
  Leukocyte recruitment is significantly impaired in the mesenteric microcirculation of cirrhotic rats. This deficiency appears to result from a reduced endothelial P-selectin, E-selectin and ICAM-1 expression. Peginterferon-alpha(2a) treatment normalizes rolling of leukocytes in cirrhotic rats by upregulation of P-selectin and E-selectin expressions, but has no influence on adhesion and extravasation possibly due to the absence of effect on ICAM-1 expression.
authors.affiliation: Department of Hepatology and Gastroenterology, Ghent University Hospital, Belgium. anja.geerts@UGent.be
authors.forename: Anja M
authors.initials: AM
authors.lastname: Geerts
authors.forename: Kin-Jip
authors.initials: KJ
authors.lastname: Cheung
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
authors.forename: Siska
authors.initials: S
authors.lastname: Mortier
authors.forename: Eline
authors.initials: E
authors.lastname: Vanheule
authors.forename: Norbert
authors.initials: N
authors.lastname: Lameire
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colle
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000187:drug effects* / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D019007:P-Selectin / Q000187:drug effects* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013152:Splanchnic Circulation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D019040:E-Selectin; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019007:P-Selectin; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a