Interactions between lipopolysaccharide and the intestinal epithelium

I ischemia often results in endotoxemia, and endotoxemia significantly increases postoperative morbidity and mortality rates in patients with ischemic intestinal disease. Even if all grossly ischemic intestine is resected, remaining intestine may be injured as a result of distention. In addition, intestine at the margins of the resection may have evidence of serosal injury and neutrophil infiltration. Endotoxemia is a result of absorption of lipopolysaccharide (LPS) from intestinal gram-negative bacteria. Gram-negative bacteria release LPS during periods of rapid proliferation and cell death. Once absorbed, LPS stimulates host cells, principally monocytes and macrophages, to produce and release endogenous mediators of inflammation, triggering pathophysiologic effects that range from mild fever to fatal septic shock. Although intestinal epithelial cells were once regarded as merely a barrier to LPS, it has recently been determined that these cells interact specifically with LPS molecules. Intestinal epithelial cells are normally exposed to high numbers of intact bacteria and high concentrations of bacterial products and form a barrier to LPS absorption and intestinal microbial invasion. As a result, intestinal epithelial cells must recognize and react to pathologic bacteria but avoid responding to the normal gastrointestinal tract flora. Inappropriate responses to normal gastrointestinal tract flora likely play a role in the development of inflammatory bowel disease. Intestinal epithelial cells are regularly exposed to LPS, and small amounts of LPS may be found in the portal blood of healthy individuals. Kupffer cells in the liver typically remove this LPS before it can reach the systemic circulation. However, if the amount of LPS in the portal blood overwhelms the liver’s mechanisms for LPS removal, then LPS will enter the systemic circulation. Circulating LPS interacts with host cells via specific cell surface receptors, and the intercalation of these molecules is considered to be an important step in the activation cascade.