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.