Disruption of the Intestinal Mucin Layer and Entry of Pancreatic Digestive Enzymes in Early Stages of Shock

Abstract

Our recent evidence shows that passage of digestive enzymes across the mucosal epithelial barrier in the intestine sets the stage for shock and multi‐organ failure. We hypothesize that the intestinal mucin layer provides a physical barrier that prevents the entry of serine proteases normally contained within the lumen of the intestine and during ischemic states the mucin layer becomes diluted allowing access of these enzymes into the intestinal wall. As a model of splanchnic ischemia we occluded the superior mesenteric and celiac arteries up to 30 minutes. We used Jejunal sections for: tissue zymography to quantify and visualize chymotrypsin entry and activity in the intestinal wall; immunohistochemistry to visualize goblet cell secreted mucin (mucin2) and membrane bound mucin (mucin13); and alcian blue staining to visualize the carbohydrate part of mucin. The results show low levels of chymotrypsin entry into the mucin layer and intestinal wall of normal non‐ischemic intestine. In contrast there is early swelling of the mucin layer and entry of chymotrypsin from the lumen of the intestine across the epithelium into the mucosa of ischemic intestine. These results indicate that dilution of the mucin layer allows the entry of powerful pancreatic digestive proteases across the intestinal barrier within minutes of ischemia. Supported by HL76180 and GM85072.