Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: an in vivo study.
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.
Geerts
Anja M
AM
Department of Hepatology and Gastroenterology, Ghent University Hospital, Belgium. anja.geerts@UGent.be
Cheung
Kin-Jip
KJ
Van Vlierberghe
Hans
H
De Vriese
An S
AS
Mortier
Siska
S
Vanheule
Eline
E
Lameire
Norbert
N
De Vos
Martine
M
Colle
Isabelle
I
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
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