INTERACTION OF SECRETORY LEUKOCYTE PROTEASE INHIBITOR WITH PROTEINASE-3

Secretory leukocyte protease inhibitor (SLPI) is a 12 kD nonglycosylat ed serine antiproteinase secreted by cells of mucosal surfaces. In hum an lung, SLPI is present in the respiratory epithelium. It is the majo r barrier to tissue destruction mediated by the polymorphonuclear leuk ocyte (PMN) serine proteinases, elastase and cathepsin G, within the u pper respiratory tract. We have recently described a third PMN serine proteinase, proteinase-3, that like elastase causes lung matrix destru ction and experimental emphysema. The current studies examine interact ions between SLPI and proteinase-3. The results show that: (1) SLPI an d its reactive-site variants have no or minimal inhibitory activity ag ainst 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 C OOH-terminal to Ala-16 in the NH2-terminal domain of SLPI.