Distribution of the human intracellular serpin protease inhibitor 8 in human tissues.
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.
Strik
Merel C
MC
VU University Medical Center, Departments of Clinical Chemistry, Amsterdam, The Netherlands. m.strik@vumc.edu
Bladergroen
Bellinda A
BA
Wouters
Dorine
D
Kisiel
Walter
W
Hooijberg
Jan Hendrik
JH
Verlaan
Angelique R
AR
Hordijk
Peter L
PL
Schneider
Pascal
P
Hack
C Erik
CE
Kummer
J Alain
JA
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
D000911:Antibodies, Monoclonal; C108403:SERPINB8 protein, human; D015843:Serpins