GROWTH-INHIBITORY EFFECT OF BOVINE LACTOFERRIN ON TOXOPLASMA-GONDII TACHYZOITES IN MURINE MACROPHAGES - ROLE OF RADICAL OXYGEN AND INORGANIC NITROGEN-OXIDE IN TOXOPLASMA GROWTH-INHIBITORY ACTIVITY

To study the effector pathway of Toxoplasma growth-inhibitory activity induced by lactoferrin in murine macrophage, the role of reactive oxy gen intermediates (O-2(-)) and inorganic nitric oxide (NO) was examine d, Production of O-2(-) was diminished in cultures of macrophages supp lemented with lactoferrin and the effect of lactoferrin was dose and t ime dependent. Production of NO was enhanced in cultures of macrophage s supplemented with interferon-gamma, but not with lactoferrin. These findings suggest that this Toxoplasma growth-inhibitory activity induc ed by lactoferrin in macrophages is not mediated by O-2(-) or NO molec ules. A competitive inhibitor of the L-arginine dependent effector pat hway, N-G-monomethyl-L-arginine (N(G)MMA), virtually abolished the inh ibitory effects induced by interferon-gamma. Similarly, the inhibitory activity induced by lactoferrin was also diminished in cultures suppl emented with N(G)MMA. From these findings, it appears that the Toxopla sma growth-inhibitory activity induced by lactoferrin in macrophages m ay be mediated by an L-arginine-dependent effector pathway that does n ot involve NO production.