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Journal of Histochemistry and Cytochemistry, Vol. 46, 497-504, April 1998, Copyright © 1998, The Histochemical Society, Inc.


ARTICLE

Immunohistochemistry of Carbonic Anhydrase Isozyme IX (MN/CA IX) in Human Gut Reveals Polarized Expression in the Epithelial Cells with the Highest Proliferative Capacity

Juha Saarnioa, Seppo Parkkilab,d,e, Anna-Kaisa Parkkilab,d, Abdul Waheedd, Matthew C. Caseyd, Xiao Yan Zhoud, Silvia Pastorekováb,d,e, Jaromir Pastoreke, Tuomo Karttunenc, Kari Haukipuroa, Matti I. Kairaluomaa, and William S. Slyd
a Departments of Surgery, University of Oulu, Oulu, Finland
b Anatomy, University of Oulu, Oulu, Finland
c Pathology, University of Oulu, Oulu, Finland
d Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St Louis, Missouri
e Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic

Correspondence to: William S. Sly, Edward A. Doisy Dept. of Biochemistry and Molecular Biology, Saint Louis U. School of Medicine, 1402 S. Grand Blvd., St Louis, MO 63104.

MN/CA IX is a recently discovered member of the carbonic anhydrase (CA) gene family that has been identified in the plasma membranes of certain 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 epithelium. The specificity of the monoclonal antibody for MN/CA IX was confirmed by Western blots and immunostaining of COS-7 cells transfected with MN/CA IX cDNA. Immunohistochemical stainings of human gut revealed prominent polarized staining for MN/CA IX in the basolateral surfaces 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 MN/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 receptor for another protein that regulates intercellular communication or cell proliferation. Furthermore, MN/CA IX has a completely conserved active site domain of CAs suggesting that it could also participate in carbon dioxide/bicarbonate homeostasis. (J Histochem Cytochem 46:497–504, 1998)

Key Words: carbonic anhydrase, gastrointestinal, gut, human, immunohistochemistry, intestine, plasma membrane


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