P-Selectin (CD62P) Expression in Liver Tissue of Biliary Atresia: A New Perspective in Etiopathogenesis

J Pediatr Gastroenterol Nutr. 2015 Nov;61(5):561-7. doi: 10.1097/MPG.0000000000000875.

Abstract

Objectives: The etiology of biliary atresia (BA) is still elusive. Inflammation plays a key role in bile duct and liver injury. The recruitment and accumulation of inflammatory cells is largely dependent on adhesion molecules. We aimed to investigate P-selectin (CD62P) expression in liver tissue in patients with BA compared with other neonatal cholestatic disorders.

Methods: The study included 63 infants with neonatal cholestasis in 2 groups: BA group (n = 32) and non-BA group (n = 31) with non-BA cholestatic disorders as controls. Demographic, clinical, laboratory, ultrasonographic, and histopathological parameters were collected. P-selectin immunostaining was performed. Immunostaining in bile duct epithelium, cellular infiltrate, and vascular endothelial cells were scored as positive or negative.

Results: The frequency of P-selectin-positive endothelium, platelets, and bile duct epithelium was significantly higher in the BA group (72%, 72%, and 63%, respectively) than in the non-BA group (32%, 16%, and 13%, respectively) with P of 0.002, <0.0001, and <0.0001, respectively. Few mononuclear cellular infiltrates in portal tract expressed P-selectin and were comparable in both groups (P = 0.932). Of interest, the platelet count was significantly higher in the BA group (532 ± 172) than in the non-BA group (406 ± 158), and 68.8% of the BA group had thrombocytosis versus 25% in the controls (P = 0.001 for both).

Conclusions: The significant expression of P-selectin in endothelium, platelets, and bile duct epithelium in patients with BA suggests a potential role for this adhesion molecule in the pathogenesis of this devastating neonatal hepatic disorder. It further suggests that platelets in BA are activated and may have a role in the inflammatory process in BA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Ducts / metabolism*
  • Bile Ducts / pathology
  • Biliary Atresia / metabolism*
  • Blood Platelets / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cholestasis / metabolism*
  • Endothelium, Vascular / metabolism
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Inflammation / metabolism*
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • P-Selectin / metabolism*
  • Thrombocytosis / complications

Substances

  • Cell Adhesion Molecules
  • P-Selectin
  • SELP protein, human