Human Intestinal Alkaline Phosphatase

HUMAN INTESTINAL ALKALINE PHOSPHATASE. Tissue expression and serum levels. ISBN 91-7174-674-9 ISSN 0346-6612 New series No 342 Ulla Domar, Department of Medical Biochemistry and Biophysics, University of Umeå, S-90187 Umeå, Sweden. Human alkaline phosphatase (ALP) comprises four isozymes, viz liver/bone/ kidney or tissue unspecific (AP), intestinal (LAP), placental (PLAP) and germ cell or PLAP-like alkaline phosphatase, with their main expression in specific tissues as indicated by their names. The isozymes are coded by different genes, but they are closely related, with more than 50% amino acid sequence homologies. Their biological function is unclear. In certain malignant and benign diseases, serum elevations of one or more of the isozymes occur, which is of diagnostic importance. In this study, the special expression of the intestinal isozyme in human tissues and sera, in normal as well as in pathological conditions, has been investigated by use of isozyme specific monoclonal antibodies. Monoclonal antibodies against the AP, IAP and PLAP isozymes were prepared, and specific assays developed, based on these monoclonal antibodies and the catalytic activity of the isozymes. By use of these assays the basal levels of all three isozymes were examined in selected normal organs. The isozymes were found to be expressed in measurable amounts in all the examined organs. IAP was immunohistochemically localized to the epithelial cells of membranes lining the ducts and tubules of the kidney, liver, pancreas and small intestine. Normal human serum contained all three isozymes. The AP isozyme constituted about 90% of the total ALP activity, the IAP isozyme less than 10% and the PLAP isozyme about 1%. Considerable interindividual variations of the serum IAP activity were observed. The serum activities of the IAP isozyme were related to the individual ABO blood group and secretor status. Non-secretors had low levels of IAP activity amounting to about one tenth of the activity in sera from blood group B or 0 secretors, while blood group A secretors had serum IAP activities in the same order as non-secretors. High individual day to day variations were observed. Fat absorption caused serum IAP to increase significantly for all persons, but it was rapidly cleared from the blood. We found that the release of IAP into the blood was linked to lipid absorption, but removal from the blood was not linked to lipoprotein clearance. Certain tumors of the testis expressed elevated levels of all three ALP isozymes. The highest activitiy of IAÌP was observed in one yolk sac tumor, in agreement with the endodermal origin of this tumor. In seminoma tissue the AP and PLAP isozymes were significantly, and IAP moderately elevated. Cirrhosis of the liver caused significantly increased serum levels of IAP besides the AP isozyme. In inflammatory diseases of the small intestine, normal serum IAP activities were observed. Kev words: Human alkaline phosphatase, intestinal alkaline phosphatase, blood, blood group, lipid, monoclonal antibody, immunohistochemistry, liver, kidney, pancreas, liver disease, inflammatory bowel disease. UMEÅ UNIVERSITY MEDICAL DISSERTATIONS New series No 342 ISSN 0346-6612 From the Department of Medical Biochemistry and Biophysics University of Umeå, Umeå, Sweden HUMAN INTESTINAL ALKALINE PHOSPHATASE Tissue expression and serum levels