help button home button Am J Pathol R & D Systems
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rosário, H. S.
Right arrow Articles by Schmid-Schönbein, G. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rosário, H. S.
Right arrow Articles by Schmid-Schönbein, G. W.
(American Journal of Pathology. 2004;164:1707-1716.)
© 2004 American Society for Investigative Pathology

Pancreatic Trypsin Increases Matrix Metalloproteinase-9 Accumulation and Activation during Acute Intestinal Ischemia-Reperfusion in the Rat

Henrique S. Rosário*{dagger}, Stephen W. Waldo{dagger}, Scott A. Becker{dagger} and Geert W. Schmid-Schönbein{dagger}

From the Department of Bioengineering,* The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California; and the Institute of Biochemistry,{dagger} Institute of Molecular Medicine, Faculty of Medicine of Lisbon, Lisbon, Portugal

Ischemia-reperfusion of the intestine produces a set of inflammatory mediators, the origin of which has recently been shown to involve pancreatic digestive enzymes. Matrix metalloproteinase-9 (MMP-9) participates in a variety of inflammatory processes including myocardial, hepatic, and pancreatic ischemia-reperfusion. In the present study, we explore the role of neutrophil-derived MMP-9 in acute intestinal ischemia-reperfusion and its interaction with pancreatic trypsin. Male Sprague-Dawley rats were subjected to 45 minutes of superior mesenteric arterial occlusion followed by 90 minutes of reperfusion. In situ zymography of the proximal jejunum reveals increased gelatinase activity in the intestinal wall after ischemia-reperfusion. Gel electrophoresis zymography and immunofluorescence co-localization suggests that this gelatinase activity is derived from MMP-9 released from infiltrating neutrophils. The role of intraluminal trypsin in this process was investigated using an in vivo isolated jejunal loop model of intestinal ischemia-reperfusion. Trypsin increased the inflammatory response after reperfusion, with an augmented neutrophil infiltration of the intestinal wall. Furthermore, trypsin stimulated a rapid conversion of neutrophil-released proMMP-9 into the lower molecular weight enzymatically active MMP-9. This process represents a powerful in vivo pathophysiological mechanism for trypsin-induced MMP-9 activation and is likely to play a central role in the development of acute intestinal inflammation and shock.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. H. Penn and G. W. Schmid-Schonbein
The intestine as source of cytotoxic mediators in shock: free fatty acids and degradation of lipid-binding proteins
Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1779 - H1792.
[Abstract] [Full Text] [PDF]

Home page
 ANGIOLOGYHome page
L. Pascarella, A. Penn, and G. W. Schmid-Schonbein
Venous Hypertension and the Inflammatory Cascade: Major Manifestations and Trigger Mechanisms
Angiology, November 1, 2005; 56(1_suppl): S3 - S10.
[Abstract] [PDF]

Home page
 ANGIOLOGYHome page
L. Pascarella, A. Penn, and G. W. Schmid-Schonbein
Venous Hypertension and the Inflammatory Cascade: Major Manifestations and Trigger Mechanisms
Angiology, November 1, 2005; 56(6_suppl): S3 - S10.
[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the American Society for Investigative Pathology.