Interaction of secretory leukocyte protease inhibitor with proteinase-3.
Secretory leukocyte protease inhibitor (SLPI) is a 12 kD nonglycosylated serine antiproteinase secreted by cells of mucosal surfaces. In human lung, SLPI is present in the respiratory epithelium. It is the major barrier to tissue destruction mediated by the polymorphonuclear leukocyte (PMN) serine proteinases, elastase and cathepsin G, within the upper respiratory tract. We have recently described a third PMN serine proteinase, proteinase-3, that like elastase causes lung matrix destruction and experimental emphysema. The current studies examine interactions between SLPI and proteinase-3. The results show that: (1) SLPI and its reactive-site variants have no or minimal inhibitory activity against proteinase-3; (2) native SLPI does not complex with proteinase-3; (3) proteinase-3 selectively degrades both native and oxidized SLPI; (4) the cleavage of SLPI by proteinase-3 occurs at the peptide bond COOH-terminal to Ala-16 in the NH2-terminal domain of SLPI.
Rao
N V
NV
University of Utah Medical Center, Salt Lake City 84132.
Marshall
B C
BC
Gray
B H
BH
Hoidal
J R
JR
D000595:Amino Acid Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008969:Molecular Sequence Data; D053146:Myeloblastin; D009504:Neutrophils / Q000201:enzymology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053146:Myeloblastin