1. A New Role for Intestinal Alkaline Phosphatase in Gut Barrier Maintenance 
Kaoru Geddes, Dana J. Philpott 
Gastroenterology 
Volume 135, Issue 1, Pages 8-12 (July 2008)
DOI: /j.gastro
Copyright © 2008 AGA Institute Terms and Conditions

2. Figure 1
ALP detoxifies LPS by dephosphorylating lipid A. LPS consists of a core polysaccharide flanked by an O-antigen group and a lipid A moiety. Lipid A mediates the toxic effects of LPS by activating TLR4 dependent signaling after sequential binding to its coreceptors, LPS binding protein (LBP), CD14 and MD-2. Uncontrolled activation of TLR4 can lead to the massive inflammation associated with septic shock. Inflammation can be controlled by ALP, which converts diphosphoryl lipid A into its inactive form, monophosphoryl lipid A. Monophosphoryl lipid A likely no longer binds to one of the coreceptors (LBP, CD14, or MD-2) and can no longer activateTLR4-dependent inflammatory responses.
Gastroenterology  , 8-12DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions

3. Figure 2
IAP detoxifies LPS to maintain gut homeostasis. Normal flora or trophic enteral feeding can maintain IAP expression. IAP detoxifies LPS to prevent inflammation and sustain barrier function, thereby maintaining homeostasis with intestinal flora. Loss of nutrition or germ-free conditions result in reduced IAP expression. This results in loss of LPS detoxification and breakdown of barrier function leading to increased susceptibility to inflammation and sepsis.
Gastroenterology  , 8-12DOI: ( /j.gastro )
Copyright © 2008 AGA Institute Terms and Conditions