Effect of L-arginine on the retention of macrophage tumoricidal activity

• Published in: The Journal of immunology (1950) Vol. 146; no. 6; pp. 1928 - 1933
• Main Authors: Takema, M, Inaba, K, Uno, K, Kakihara, K, Tawara, K, Muramatsu, S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.03.1991; American Association of Immunologists
• Subjects: Animals; Arginine - physiology; Biological and medical sciences; Cell Survival; Cells, Cultured; Cytotoxicity, Immunologic - drug effects; Cytotoxicity, Immunologic - physiology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Indomethacin - pharmacology; Macrophage Activation - immunology; Macrophages - drug effects; Macrophages - immunology; Male; Mice; Mice, Inbred C3H; Myeloid cells: ontogeny, maturation, markers, receptors; Nitrogen Dioxide - metabolism; Polynuclears; Tumor Cells, Cultured - immunology; Antineoplastic agent; Culture medium; Cell culture; Rodentia; Cytotoxicity; Biological activity; Dose activity relation; Vertebrata; Mammalia; Arginine; Mouse; Cell death; Tumor; Viability; Macrophage
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.146.6.1928

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.