Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells.
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.
Zaninovic
V
V
Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and University of California, Los Angeles, California 90073, USA.
Gukovskaya
A S
AS
Gukovsky
I
I
Mouria
M
M
Pandol
S J
SJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002108:Ceruletide / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000502:physiology; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D002108:Ceruletide; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde