It may not be intestinal, but tissue non-specific alkaline phosphatase (Response)

As mentioned by Martinez-Augustin et al, we found reduced levels for intestinal alkaline phosphatase (AP) mRNA in rats with dextran sulfate sodium (DSS)-induced colitis and in patients with ulcerative colitis.1 In the same paper we show a reduced enzyme activity along the intestinal epithelium in sections from rats with DSS-induced colitis (figure 6K of Tuin et al1). There is no contradiction in this. However, as also noted by Martinez-Augustin et al, this decline in intestinal AP was associated with an increased staining for AP in infiltrating cells. It is indeed tempting to speculate that the augmentation of one isoenzyme serves to compensate the loss of another one. If this is the case, the function of AP must be important. In 1997 we proposed that AP plays an important role in the defence system against lipopolysaccharide (LPS); we found that AP can dephosphorylate the lipid A moiety of LPS, thereby detoxifying this bacterial product.2 We suggested that this activity might even be a physiological role for this enzyme, this sugggestion being based in part on the fact that AP dephosphorylated LPS at physiological pH levels (pH 7.4) in contrast to the dephosphorylation of all other substrates (pH optimum >10) and that the localisation of the enzyme in most cases perfectly fits with its proposed role. In particular the co-localisation of AP with the LPS receptor CD14 within neutrophils3 provides fuel for this notion. Recent publications by Goldberg and Hodin et al support this hypothesis.4 So, accumulating evidence suggests that AP plays a key role in the intestinal wall. It would be an important step to definitely unravel a role for this enzyme that has been extensively studied ever since 1934, whose presence is so ubiquitous in nearly all organs of the body, whose activity profoundly changes during various diseases, yet whose function is so utterly obscure.