Publicação
Matrix metalloproteinase-9 and pancreatic trypsin in the intestinal wall : a contribution to the understanding of intestinal ischemia-reperfusion
| Resumo: | 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. |
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| Autores principais: | Rosário, Henrique Baptista Colaço Sobral do, 1971- |
| Assunto: | Intestino grosso Intestino delgado Isquémia Traumatismo por reperfusão Metaloproteinase 9 da matriz Tripsina Teses de doutoramento - 2009 |
| Ano: | 2009 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | 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. |
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