Doxycycline in the protection of serum alpha-1-antitrypsin from human neutrophil collagenase and gelatinase.
The concentration of doxycycline required to inhibit 50% (50% inhibitory concentration for serpinase activity) of alpha-1-antitrypsin degradation by purified neutrophil collagenase was found to be approximately 20 microM, a value similar to the 50% inhibitory concentration of doxycycline required to inhibit collagen degradation by neutrophil collagenase. Doxycycline also efficiently inhibited phorbol myristate acetate-triggered neutrophil-mediated degradation of alpha-1-antitrypsin. This suggests that doxycycline can protect alpha-1-antitrypsin from collagenase and gelatinase in the presence of other proteases and biologically active molecules that are released by triggered neutrophils. The protection of a body's alpha-1-antitrypsin shield from serpinolytic activity of collagenase and matrix metallproteinases can result in inhibition of serine proteases such as neutrophil elastase. Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase.
Department of Periodontology, Helsinki University, Finland.
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T
Sorsa
O
O
Lindy
Y T
YT
Konttinen
K
K
Suomalainen
T
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Ingman
H
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Saari
S
S
Halinen
H M
HM
Lee
L M
LM
Golub
J
J
Hall
D017364:Collagenases / Q000097:blood; D004318:Doxycycline / Q000494:pharmacology*; D018093:Gelatinases; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010434:Pepsin A / Q000037:antagonists & inhibitors* / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000187:drug effects* / Q000378:metabolism
D061965:Matrix Metalloproteinase Inhibitors; D000515:alpha 1-Antitrypsin; D010434:Pepsin A; D017364:Collagenases; D018093:Gelatinases; D004318:Doxycycline; D013755:Tetradecanoylphorbol Acetate