Distribution of the Human Intracellular Serpin Protease Inhibitor 8 in Human TissuesMerel C. Strika, Bellinda A. Bladergroena, Dorine Woutersa, Walter Kisielc, Jan Hendrik Hooijberga, Angelique R. Verlaanb, Peter L. Hordijke, Pascal Schneiderd, C. Erik Hacka,f, and J. Alain Kummerb,da VU University Medical Center, Departments of Clinical Chemistry, Amsterdam, The Netherlands b Pathology, Amsterdam, The Netherlands c Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico d Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, Epalinges, Switzerland e CLB, Departments of Experimental Immunohematology, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands f Immunopathology, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands Correspondence to: Merel C. Strik, Dept. of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. E-mail: m.strik@vumc.nl Ovalbumin-like serine protease inhibitors are mainly localized intracellularly and their in vivo functions are largely unknown. To elucidate their physiological role(s), we studied the expression of one of these inhibitors, protease inhibitor 8 (PI-8), in normal human tissues by immunohistochemistry using a PI-8-specific monoclonal antibody. PI-8 was strongly expressed in the nuclei of squamous epithelium of mouth, pharynx, esophagus, and epidermis, and by the epithelial layer of skin appendages, particularly by more differentiated epithelial cells. PI-8 was also expressed by monocytes and by neuroendocrine cells in the pituitary gland, pancreas, and digestive tract. Monocytes showed nuclear and cytoplasmic localization of PI-8, whereas neuroendocrine cells showed only cytoplasmic staining. In vitro nuclear localization of PI-8 was confirmed by confocal analysis using serpin-transfected HeLa cells. Furthermore, mutation of the P1 residue did not affect the subcellular distribution pattern of PI-8, indicating that its nuclear localization is independent of the interaction with its target protease. We conclude that PI-8 has a unique distribution pattern in human tissues compared to the distribution patterns of other intracellular serpins. Additional studies must be performed to elucidate its physiological role. (J Histochem Cytochem 50:14431453, 2002) Key Words: serpin, human, nucleus, PI-8, immunohistochemistry
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