title: Distribution of the human intracellular serpin protease inhibitor 8 in human tissues.
abstract: 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 P(1) 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.
authors.affiliation: VU University Medical Center, Departments of Clinical Chemistry, Amsterdam, The Netherlands. m.strik@vumc.edu
authors.forename: Merel C
authors.initials: MC
authors.lastname: Strik
authors.forename: Bellinda A
authors.initials: BA
authors.lastname: Bladergroen
authors.forename: Dorine
authors.initials: D
authors.lastname: Wouters
authors.forename: Walter
authors.initials: W
authors.lastname: Kisiel
authors.forename: Jan Hendrik
authors.initials: JH
authors.lastname: Hooijberg
authors.forename: Angelique R
authors.initials: AR
authors.lastname: Verlaan
authors.forename: Peter L
authors.initials: PL
authors.lastname: Hordijk
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: J Alain
authors.initials: JA
authors.lastname: Kummer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009490:Neurosecretory Systems / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D015843:Serpins / Q000276:immunology / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C108403:SERPINB8 protein, human; D015843:Serpins