80年代中期,Hibbs等研究人员通过离体实验证实,哺乳动物的巨噬细胞受细菌产物脂多糖(Lipopolysaccharide LPS)刺激后,能产生NO_2~-和NO_3~-。随后研究发现NO_2~-和NO_3~-的产生与巨噬细胞的毒性效应分子功能有关,L-精氨酸是巨噬细胞产生NO_2~-和NO_3~-的唯一底物,并且L-精氨酸的结构类似物NMMA(NG-Monomethyl-L-arginine)可强烈抑制NO_2~-和NO_3~-的产生。由于NO_2~-和NO_3~-本身不具有细胞毒性作用,因此推测NO_2~-和NO_3~-产生的过程中 In the mid-1980s, researchers from Hibbs et al. confirmed that ex vivo mammalian macrophages were stimulated by lipopolysaccharide (LPS) to produce NO_2~- and NO_3~-. Subsequent studies found that the production of NO_2~- and NO_3~- is related to the toxic effector function of macrophages. L-arginine is the sole substrate for the production of NO_2~- and NO_3~ by macrophages, and L-arginine The structural analog NMMA (NG-Monomethyl-L-arginine) strongly inhibited the production of NO_2~- and NO_3~-. Since NO_2~- and NO_3~- do not have cytotoxicity by themselves, it is speculated that the production of NO_2~- and NO_3~-