Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation

Clin Biochem. 2002 Sep;35(6):455-61. doi: 10.1016/s0009-9120(02)00330-2.


Intestinal alkaline phosphatase (AP), as a host defense factor, was first investigated in vivo using rats orally exposed to lipopolysaccharide (LPS). After the oral administration of LPS to rats, serum LPS content was increased within 2 hr and then decreased to 6 hr. In contrast, when L-phenylalanine (L-Phe), an inhibitor of intestinal-type AP isozymes, was simultaneously administered with LPS, serum LPS content significantly increased from 1 hr and the area under the concentration-time curve of serum LPS was augmented approximately 2-fold, suggesting that APs in the gastrointestinal tract reduced serum LPS content. In addition, LPS toxicity diminished by a treatment in vitro with intestinal APs, were recovered by the treatment in the co-presence of L-Phe. In the experiment using human aortic endothelial cells (HAECs), we observed that the cell viability decreased in a dose-dependent manner of LPS-exposure, and the LPS dose, exhibiting 50% viability of the cells, was 0.05 microg/ml. When the cells were exposed to LPS pretreated with 50 nIU/ml of intestinal AP at pH 10.0 and 8.0, the 50% viability was at 2.0 microg/ml of LPS. These results strongly suggest that the APs reduced the toxicity of LPS, as a host defense factor against LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alkaline Phosphatase / metabolism*
  • Animals
  • Antigens, Neoplasm / metabolism
  • Blotting, Western
  • Duodenum / drug effects
  • Duodenum / enzymology
  • GPI-Linked Proteins
  • In Vitro Techniques
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / blood
  • Lipopolysaccharides / metabolism*
  • Lipopolysaccharides / toxicity*
  • Male
  • Nitric Oxide / analysis
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Phosphorylation
  • Rats
  • Rats, Wistar


  • Antigens, Neoplasm
  • GPI-Linked Proteins
  • Lipopolysaccharides
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • ALPI protein, human
  • Alkaline Phosphatase