Inhibition of human neutrophil and Pseudomonas elastases by the amyloid P-component: a constituent of elastic fibers and amyloid deposits.
The amyloid P-component (AP), a ubiquitous component of amyloid fibrils, is also a plasma protein and a connective tissue constituent. Its proximity to elastin, in particular, suggested that AP might serve to protect elastic tissue from hydrolytic enzymes. The inhibition of pancreatic elastase by AP has been reported. In the present study, the effects of AP on human neutrophil elastase and Pseudomonas elastase were investigated, and AP was shown to interfere with the cleavage of soluble elastin. As indicated by Michaelis-Menten analysis, AP is acting as a noncompetitive inhibitor. C-reactive protein, which is structurally similar to AP, had no effect on either elastase. AP was also found to inhibit the degradation of secondary amyloid fibrils by neutrophil elastase when these structures were first partially purified and then reexposed to AP. AP's ability to inhibit elastase was compared with alpha-1 antitrypsin in the presence and absence of oxidizing agents. These substances, which are released by inflammatory cells, are known to abrogate alpha-1 antitrypsin's anti-protease capacity. This contributes to elevated levels of free proteases in the circulation and extravascular spaces during severe inflammation. AP is not susceptible to oxidation and remains a functional inhibitor under these conditions. The potential role of AP as an elastase inhibitor is discussed.
Vachino
G
G
Department of Geographic Medicine and Infectious Diseases, Tufts New England Medical Center, Boston, MA 02111.
Heck
L W
LW
Gelfand
J A
JA
Kaplan
M M
MM
Burke
J F
JF
Berninger
R W
RW
McAdam
K P
KP
D000682:Amyloid / Q000378:metabolism; D002097:C-Reactive Protein / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D011549:Pseudomonas / Q000201:enzymology*; D000683:Serum Amyloid P-Component / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D000682:Amyloid; D000683:Serum Amyloid P-Component; D000515:alpha 1-Antitrypsin; D002097:C-Reactive Protein; D010196:Pancreatic Elastase