ABSTRACT
The in vitro activation of murine macrophages by horseradish peroxidase (HRP) induced nitric oxide production in a dose-dependent manner, and increased the induction of NO-synthase by LPS. Nitrite production after HRP stimulation was inhibited by NG-monomethyl-L-arginine (NMMA), a specific inhibitor of NO-synthase. Equivalent amounts of nitrite were obtained with native and heat-inactivated HRP. High concentrations of mannose inhibited nitric oxide production, while the HRP inhibitor 3-aminotyrosine did not. Glycosylated serum albumin derivatives also induced murine macrophage NOS, probably by an interaction between carbohydrates and their specific cell membrane receptors. The inability of HRP apoprotein to stimulate NO production, and the specific inhibition of HRP-mediated activation of macrophages by hemin suggests that the heme moiety of this enzyme is involved in NO-synthase induction.
