IMMUNOHISTOCHEMISTRY OF CARBONIC-ANHYDRASE ISOZYME-IX (MN CA-IX) IN HUMAN GUT REVEALS POLARIZED EXPRESSION IN THE EPITHELIAL-CELLS WITH THEHIGHEST PROLIFERATIVE CAPACITY/

MN/CA IX is a recently discovered member of the carbonic anhydrase (CA ) gene family that has been identified in the plasma membranes of cert ain tumor and epithelial cells and found to promote cell proliferation when transfected into NIH3T3 cells. This study presents localization of MN/CA IX in human gut and compares its distribution to those of CA I, II, and IV, which are known to be expressed in the intestinal epith elium. The specificity of the monoclonal antibody for MN/CA IX was con firmed by Western blots and immunostaining of COS-7 cells transfected with MN/CA IX cDNA. Immunohistochemical stainings of human gut reveale d prominent polarized staining for MN/CA IX in the basolateral surface s of the enterocytes of duodenum and jejunum, the reaction being most intense in the crypts. A moderate reaction was also seen in the crypts of ileal mucosa, whereas the staining became generally weaker in the large intestine. The results indicate isozyme-specific regulation of M N/CA IX expression along the cranial-caudal axis of the human gut and place the protein at the sites of rapid cell proliferation. The unique localization of MN/CA IX on the basolateral surfaces of proliferating crypt enterocytes suggests that it might serve as a ligand or a recep tor for another protein that regulates intercellular communication or cell proliferation. Furthermore, MN/CA IX has a completely conserved a ctive site domain of CAs suggesting that it could also participate in carbon dioxide/bicarbonate homeostasis.