Submitted on May 14, 2004
Accepted on August 2, 2004
MEMBRANE-BOUND ICAM-1 IS UPREGULATED BY TRYPSIN AND CONTRIBUTES TO LEUKOCYTE MIGRATION IN ACUTE PANCREATITIS
Werner Hartwig1, Jens Werner1, Andrew L. Warshaw2, Bozena Antoniu2, Carlos Fernandez-del Castillo2, Marth-Maria Gebhard3, Waldemar Uhl1, and Markus W. Buchler1*
1 Departments of General Surgery, University of Heidelberg, Heidelberg, Germany
2 Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, USA
3 Department of Experimental Surgery, University of Heidelberg, Heidelberg, Germany
* To whom correspondence should be addressed. E-mail: markus_buechler{at}med.uni-heidelberg.de.
In acute pancreatitis, intercellular adhesion molecule-1 (ICAM-1) is upregulated in various
organs and contributes to the development of organ injury. To investigate the effects of
pancreatic proteases on ICAM-1 expression and their role in the early process of leukocyte
migration, human umbilical vein endothelial cells (HUVECs) were incubated with serum
subjected to limited trypsin digestion and wistar rats were injected with trypsin. Significant
upregulation of membrane bound ICAM-1 was seen on HUVECs incubated with trypsinated
serum. Likewise, soluble ICAM-1 increased in the supernatant of HUVECs. Changes of
membrane bound ICAM-1 and soluble ICAM-1 were maximal with high concentrations of
trypsin. HUVECs incubated with TNF-alpha (positive control) showed similar changes. In the
pancreas and lungs of animals infused with trypsin, ICAM-1 as well as leukocyte sequestration
was increased compared to controls. Reflecting the relevance of protease-induced ICAM-1
expression in leukocyte migration, leukocyte-endothelium interaction, as assessed by intravital
microscopy, was markedly increased by trypsin. Inhibition of ICAM-1 ameliorated these changes
significantly. In conclusion, trypsinated serum induces the upregulation of both membrane bound
ICAM-1 on endothelial cells and soluble ICAM-1. These changes contribute to the early steps of
leukocyte migration in acute pancreatitis. The role of soluble ICAM-1 remains to be investigated.
