Varesio L, Clayton M, Blasi E, Ruffman R, Radzioch D
Immunobiology Section, National Cancer Institute, Frederick, MD 21701-1013.
J Immunol. 1990 Dec 15;145(12):4265-71.
We have studied the effects of picolinic acid, a product of tryptophan degradation, on the activation of mouse peritoneal macrophages (M phi). Picolinic acid acts synergistically with IFN-gamma in activating M phi from C57BL/6 mice. Moreover, M phi from C3H/HeJ mice and C3H/HeN that do not become cytotoxic in response to IFN-gamma alone could be fully activated by exposure to picolinate plus IFN-gamma. These results indicate that picolinic acid is a potent costimulator of M phi activation that functions as a second signal. Inasmuch as we have previously demonstrated that the activation of cytotoxic M phi correlates with specific changes in ribosomal RNA (rRNA), we investigated whether picolinic acid could modify M phi RNA metabolism. Picolinic acid inhibited the synthesis of total M phi RNA, the accumulation of newly synthesized 28S rRNA, and augmented the steady state levels of rRNA precursors (pre-rRNA). These changes in RNA metabolism were similar to those previously described in murine M phi activated in vitro or in vivo to express tumoricidal activity. These results demonstrate that picolinic acid is a potent, biologic M phi second signal, suggest that the changes in rRNA are causally connected with the expression of tumoricidal activity, and suggest the existance of an autocrine effect mediated by picolinic acid.
我们研究了色氨酸降解产物吡啶甲酸对小鼠腹腔巨噬细胞（M phi）激活的影响。吡啶甲酸与干扰素-γ协同作用，激活C57BL/6小鼠的M phi。此外，单独对干扰素-γ无细胞毒性反应的C3H/HeJ小鼠和C3H/HeN小鼠的M phi，通过暴露于吡啶甲酸盐加干扰素-γ可被完全激活。这些结果表明，吡啶甲酸是一种有效的M phi激活共刺激因子，作为第二信号发挥作用。鉴于我们之前已经证明细胞毒性M phi的激活与核糖体RNA（rRNA）的特定变化相关，我们研究了吡啶甲酸是否能改变M phi的RNA代谢。吡啶甲酸抑制了M phi总RNA的合成、新合成的28S rRNA的积累，并提高了rRNA前体（前体rRNA）的稳态水平。RNA代谢的这些变化与之前在体外或体内激活以表达杀肿瘤活性的小鼠M phi中描述的变化相似。这些结果表明，吡啶甲酸是一种有效的生物M phi第二信号，表明rRNA的变化与杀肿瘤活性的表达有因果关系，并表明存在由吡啶甲酸介导的自分泌效应。
