Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells

Am J Physiol Gastrointest Liver Physiol. 2000 Oct;279(4):G666-76. doi: 10.1152/ajpgi.2000.279.4.G666.

Abstract

Neutrophil infiltration into the pancreas is a key event in pancreatitis. Here we show that intercellular adhesion molecule-1 (ICAM-1), which regulates neutrophil adhesion, is present on rat pancreatic acinar cells, is upregulated by a hormone (cerulein) and mediates direct binding of neutrophils to acinar cells. ICAM-1 was upregulated in pancreas of rats with experimental pancreatitis induced by supramaximal doses of cerulein. Furthermore, cerulein time and dose dependently stimulated expression of ICAM-1 mRNA and protein in isolated pancreatic acinar cells. Inhibitory analysis showed that activation of transcription factor nuclear factor-kappaB (NF-kappaB) was involved in ICAM-1 upregulation by cerulein, but NF-kappaB did not mediate basal expression of ICAM-1 mRNA in acinar cells. With an adhesion assay, we found that neutrophils bind to isolated pancreatic acinar cells and that cerulein upregulates the extent of adhesion. Neutralizing ICAM-1 antibody blocked neutrophil binding to both control and cerulein-stimulated acinar cells, suggesting ICAM-1 involvement in this adhesion. Thus the acinar cell is capable of targeting neutrophils to its surface, a process that may be important for inflammatory and cell death responses in pancreatitis and other pancreatic disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Ceruletide / pharmacology*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects*
  • Intercellular Adhesion Molecule-1 / genetics*
  • Intercellular Adhesion Molecule-1 / physiology
  • Kinetics
  • Leupeptins / pharmacology
  • Male
  • Neutrophils / physiology*
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / physiology*
  • Pancreatitis / chemically induced
  • Pancreatitis / genetics
  • Pancreatitis / physiopathology
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects

Substances

  • Cysteine Proteinase Inhibitors
  • Leupeptins
  • RNA, Messenger
  • Intercellular Adhesion Molecule-1
  • Ceruletide
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde