The human alkaline phosphatases: What we know and what we don't know

Structure of the human liver/bone/kidney alkaline phosphatase gene.

Under conditions of starvation and disease, the gut barrier becomes impaired, and trophic feeding to prevent gut mucosal atrophy has become a standard treatment of critically ill patients. However, the mechanisms responsible for the beneficial effects of enteral nutrition have remained a mystery. Using in vitro and in vivo models, we demonstrate that the brush–border enzyme, intestinal alkaline phosphatase (IAP), has the ability to detoxify lipopolysaccharide and prevent bacterial invasion across the gut mucosal barrier. IAP expression and function are lost with starvation and maintained by enteral feeding. It is likely that the IAP silencing that occurs during starvation is a key component of the gut mucosal barrier dysfunction seen in critically ill patients.

https://www.pnas.org/content/pnas/105/9/3551.full.pdf

Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition

Immunohistochemical staining is the detection of Techniques in which the primary antibodies specific antigens in tissue sections through the use of specific for the antigen of interest are labeled with an enzyme antibodies that are labeled so that the sites of antibody are termed direct methods (Fig. la). In direct immuattachment become microscopically visible. Immu- nostains, the antiserum is incubated on the tissue folnohistochemistry has been used for diagnosis of dis- lowed by addition of an enzyme substrate that causes eases associated with autoantibodies, tumors, immune the deposition of an insoluble colored reaction product complex deposition, and for the detection of micro- at the sites of antibody binding in the tissues. This organisms causing infectious diseases. 9,18,26,31 Until recently, most immunohistochemical stains have used fluorescein dye-labeled antibodies on fresh or frozen tissue specimens. 10 These methods produce a labile stain that is visible only with an ultraviolet microscope. Enzyme-labeled antibodies and methods applicable to tissues fixed in standard fixatives such as formalin have been more recently described. 16,24 These techniques have added a new dimension to diagnostic pathology by creating permanent stains demonstrating the distribution of antigens visible with ordinary light microscopy. This paper summarizes some of the techniques, the technical problems, and the limitations of the application of enzyme immunohistochemical stains on fixed tissues in diagnostic veterinary pathology. Recently, automated systems for performing immunohistochemical stains have been developed, 7 and the use of 1 of these systems is described. Immunohistochemical staining methods

https://journals.sagepub.com/doi/pdf/10.1177/104063879100300128

Technical considerations for developing enzyme immunohistochemical staining procedures on formalin-fixed paraffin-embedded tissues for diagnostic pathology.

http://www.jbc.org/content/261/7/3112.full.pdf

Molecular cloning and sequence analysis of human placental alkaline phosphatase.

Alkaline phosphatases [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] have been examined in liver, bone, kidney, intestine, and placenta from nine mammalian species by quantitative inhibition and thermostability studies and compared with alkaline phosphatases in the corresponding human tissues. In humans, three kinds of alkaline phosphatase can be sharply differentiated by these methods, one occurring in liver, bone, and kidney, one in intestine, and one in placenta. They are evidently determined by separate gene loci. In the mammals only two sorts of alkaline phosphatase were found: one, which occurs in liver, bone, kidney, and also placenta, corresponds to the human liver/bone/kidney enzyme and the other corresponds to the human intestinal enzyme. The findings support our earlier proposal that the expression of a distinctive type of alkaline phosphatase in human placenta is the consequence of a late evolutionary event which occurred subsequent to the divergence of the evolutionary lineage leading to humans from the various lineages leading to other mammalian species. The concentrations of the inhibitors, phenylalanine, homoarginine, phenylalanylglycylglycine, and levamisole, required to give 50% inhibition, [I50], of the liver/bone/kidney/placental (nonhuman) alkaline phosphatases showed no significant variation among the species. However, the [I50] values for the intestinal enzyme varied among species to a much greater extent. This implies that in the liver/bone/kidney/placental (nonhuman) alkaline phosphatase the structures of the binding sites for these inhibitors have been highly conserved during mammalian evolution, but there has been much greater divergence of these structures in the evolution of intestinal alkaline phosphatases.

Expression of alkaline phosphatase loci in mammalian tissues

A search for trace expression of placental-like alkaline phosphatase in non-malignant human tissues: demonstration of its occurrence in lung, cervix, testis and thymus.

Alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3131] in placenta, intestine, liver, kidney, bone, and lung from a variety of primate species has been characterized by quantitative inhibition, thermostability, and immunological studies Characteristic human placental-type alkaline phosphatase occurs in placentas of great apes (chimpanzee and orangutan) but not in placentas of other primates, including gibbon It is also present in trace amounts in human lung but not in lung or other tissues of various Old and New World monkeys However, a distinctive alkaline phosphatase resembling it occurs in substantial amounts in lungs from Old World monkeys but not New World monkeys It appears that duplication of alkaline phosphatase genes and mutations of genetic elements controlling their tissue expression have occurred relatively recently in mammalian evolution

Caprice E. Rogers

Papers

Expression of alkaline phosphatase loci in mammalian tissues

A search for trace expression of placental-like alkaline phosphatase in non-malignant human tissues: demonstration of its occurrence in lung, cervix, testis and thymus.

Evolution of alkaline phosphatases in primates.

Differentiation of immunochemically related enzymes in different primate species by monoclonal antibodies