Serine-protease inhibitors modulate nitric oxide-synthase activity of alveolar macrophages.
Immunostimulated peritoneal macrophages of mice and rat have been demonstrated to produce L-arginine-derived nitrogen oxides. This metabolic pathway has also recently been found in rat alveolar macrophages and is suggested to play a certain role in lung injury. In vitro nitrite production from alveolar macrophages stimulated in vitro with lipopolysaccharide and recombinant interferon-gamma was inhibited by the addition of the irreversible serine-protease inhibitors, N-tosyl-L-phenylalanine chloromethyl-ketone (3 x 10(-7)-3 x 10(-4) M) and N-tosyl-L-lysine chloromethyl-ketone (3 x 10(-7)-3 x 10(-4) M) in a concentration-dependent manner. Two reversible inhibitors, N-alpha-p-tosyl-L-arginine methyl ester hydrochloride and benzoyltyrosine ethyl ester, were also effective but to a lesser extent. These antiproteases provide an opportunity to study the modulating influence on this recently discovered inflammatory pathway in alveolar phagocytic cells.
Jorens
P G
PG
Department of Respiratory Medicine, University of Antwerp (UIA), Belgium.
Van Overeld
F J
FJ
Bult
H
H
Vermeire
P A
PA
Herman
A G
AG
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D009573:Nitrites; D015842:Serine Proteinase Inhibitors; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases