Neutrophil adhesion is impaired in rat model of cholestasis.

Abstract

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. Neutrophil function was assessed using both in vivo and in vitro techniques. 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 values, 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. 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.