Gastroenterology

Gastroenterology

Volume 109, Issue 3, September 1995, Pages 923-932
Gastroenterology

Neutrophil adhesion is impaired in a rat model of cholestasis

https://doi.org/10.1016/0016-5085(95)90403-4Get rights and content

Abstract

Background & Aims: A high incidence of septic complications has been documented in patients with obstructive jaundice undergoing surgery. Because neutrophils play a central role in the response to infection, the aim of this study was to investigate neutrophil function in a rat model of acute cholestasis induced by bile duct resection. Methods: Neutrophil function was assessed using both in vivo and in vitro techniques. Results: The inflammatory response was defective in vivo in bile duct-resected (BDR) rats compared with sham-resected controls. Furthermore, proinflammatory stimulus-induced neutrophil adherence and emigration from mesenteric venules, assessed in vivo using intravital microscopy, was attenuated in BDR vs. sham rats. Neutrophils isolated from BDR and sham rats studied in vitro adhered to a rat biological substratum similarly. However, stimulated neutrophil adherence was eliminated in the presence of BDR but not sham plasma. Similar findings were observed using plasma obtained from a patient with obstructive cholestasis. Experiments performed to further characterize this antiadhesive factor in BDR plasma suggest that the factor is probably a heat-stable glycoprotein. Conclusions: Cholestasis in the rat is associated with a defective acute inflammatory response that appears, at least in part, to be caused by a constituent of cholestatic plasma that is antiadhesive to neutrophils.

References (36)

  • RC Woodman et al.

    The effects of human neutrophil elastase (HNE) on neutrophil function in vitro and in inflamed microvessels

    Blood

    (1993)
  • MG Swain et al.

    Sympathetic nerves, but not the adrenal gland, contribute to elevated plasma levels of met-enkephalin in rats with acute cholestatic hepatitis

    Regul Pept

    (1993)
  • MG Swain et al.

    Endogenous opioids accumulate in plasma of bile duct-resected rats

    Gastroenterology

    (1992)
  • CP Armstrong et al.

    Surgical experience of deeply jaundiced patients with bile duct obstruction

    Br J Surg

    (1984)
  • MRB Keighley et al.

    Hazards of surgical treatment due to microorganisms in the bile

    Surgery

    (1974)
  • JI Benkharn et al.

    Septic complications of percutaneous transhepatic biliary drainage

    Am J Surg

    (1984)
  • PT Roughneen et al.

    Impaired nonspecific cellular immunity in experimental cholestasis

    Ann Surg

    (1987)
  • R Levy et al.

    Increased neutrophil function induced by bile duct ligation in a rat model

    Hepatology

    (1993)
  • Cited by (31)

    • Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: An in vivo study

      2007, Journal of Hepatology
      Citation Excerpt :

      A deficiency in one of the three steps of leukocyte recruitment can result in an inability of neutrophils to infiltrate in a region of inflammation. Impaired leukocyte recruitment has been reported previously in mesenteric venules of portal hypertensive rats [20,21] and in a model of acute cholestasis [22]. These findings support further the hypothesis of an altered anti-bacterial response in the splanchnic circulation.

    View all citing articles on Scopus

    Supported by grants from the Alberta Heritage Foundation for Medical Research (AHFMR), the Canadian Liver Foundation, and the Crohn's and Colitis Foundation. Dr. Kubes is an AHFMR and Medical Research Council scholar, and Dr. Swain is an AHFMR Clinical Investigator. Dr. Kanwar is supported by a Canadian Liver Foundation Studentship and Dr. Tjandra by a Canadian Liver Foundation Summer Studentship.

    The authors thank M. Maric and P. Reinhardt for expert technical assistance and Dr. G. May for referral of patient B.L. and for performing the endoscopic retrograde cholangiopancreatography.

    View full text