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Injurious and Protective Mechanisms in the Gut

Interaction of PAF, Phospholipase A2, Eicosanoids, and Nitric Oxide Synthase
  • Wei Hsueh
  • Xiao-di Tan
  • Xiao-wu Qu
  • Xiao-ming Sun
  • F. Gonzalez-Crussi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 407)

Abstract

Inflammation, a process necessary for destroying invading organisms, may cause tissue damage in the host. The intestinal mucosa is especially at risk due to its constant exposure to abundant bacteria flora (1012 organisms/g). Invasion by bacteria or their products, such as endotoxin (LPS), may elicit the release of inflammatory mediators that synergize with each other and induce one another’s production, thereby leading to eventual tissue destruction. Mild inflammatory reactions may be self-limiting, due to protective mechanisms intrinsic to the intestinal mucosa. Severe insults overwhelm the protective mechanism resulting in irreversible intestinal necrosis. This paper will discuss some interactions between pro-inflammatory lipid mediators and protective mediators, e. g., PAF, eicosanoids, phospholipase A2 (PLA2), and nitric oxide (NO), in an experimental model of intestinal injury. PAF (platelet-activating factor, paf-acether), an endogenous phospholipid mediator (for review, see Refs. 1–3), is used to elicit experimental injury because PAF has been shown to be the endogenous mediator for LPS-induced bowel injury (4), and has been implicated in necrotizing enterocolitis (reviewed in ref. 5), and other intestinal inflammatory lesions (reviewed in ref. 6). PAF is synthesized by intestinal epithelial cells (7), as well as various inflammatory cells and endothelial cells (for review, see Refs. 1–3) which are resident cells in the lamina propria of the intestinal mucosa. Systemic administration of PAF induces potent pathophysiological changes mimicking circulatory shock (reviewed in Refs. 1–3), and intestinal necrosis (8). LPS and PAF act synergistically to induce shock and bowel necrosis (8). Combined LPS and TNF-a administration also cause bowel necrosis (9), which is probably mediated by endogenous PAF (9).

Keywords

Nitric Oxide Intestinal Injury Bowel Necrosis Endogenous Mediator cNOS Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Wei Hsueh
    • 1
  • Xiao-di Tan
    • 1
  • Xiao-wu Qu
    • 1
  • Xiao-ming Sun
    • 1
  • F. Gonzalez-Crussi
    • 1
  1. 1.Department of PathologyChildren’s Memorial Hospital, Northwestern Universuty Medical SchoolChicagoUSA

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