Effect of L-arginine on the retention of macrophage tumoricidal activity.
It has been reported that the tumoricidal activity of macrophages (M phi) depends on L-arginine and that L-arginine metabolites such as reactive nitrogen intermediates alter M phi physical capacities. The aim of this report is to investigate the dose-related effect of L-arginine on the expression and retention of M phi tumoricidal activity. Cytotoxicity of M phi activated by IFN-gamma plus LPS was detected in the presence of about 0.1 mM or more of L-arginine. This paralleled the NO2- production in the presence, but not in the absence, of L-arginine. On the other hand, activated M phi were destined to die and lost their tumoricidal activity with time in the presence of 0.3 mM or more L-arginine. They retained, however, considerable activity in the absence or presence of 0.15 mM L-arginine. This retention of M phi cytotoxicity was longer when M phi were preactivated by 100 ng/ml than 10 ng/ml of LPS in combination with IFN-gamma. Addition of indomethacin, an inhibitor of prostaglandin production, did not prevent the decay of M phi cytotoxicity but rather facilitated it even in the absence of L-arginine. Regardless of indomethacin, consecutive stimulation with LPS or LPS plus IFN-gamma during culture was effective in maintaining the tumoricidal activity at a high level. In addition, we found that M phi which had lost tumoricidal activity during culture in L-arginine deficient medium could be reactivated by LPS to attack tumor target cells.
Takema
M
M
Shionogi Research Laboratories, Osaka, Japan.
Inaba
K
K
Uno
K
K
Kakihara
K
K
Tawara
K
K
Muramatsu
S
S
D000818:Animals; D001120:Arginine / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000502:physiology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009585:Nitrogen Dioxide / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology*
D001120:Arginine; D009585:Nitrogen Dioxide; D007213:Indomethacin