Albina J E, Caldwell M D, Henry W L, Mills C D
Department of Surgery, Rhode Island Hospital, Providence.
J Exp Med. 1989 Mar 1;169(3):1021-9. doi: 10.1084/jem.169.3.1021.
Sites of inflammation with prominent macrophage infiltration, such as wounds and certain tumors, are uniquely deficient in free arginine. The effects of arginine availability on macrophage physiology were investigated. When cultured in media containing less than 0.1 mM L-arginine, rat resident peritoneal macrophages exhibited enhanced spreading, tumor cytotoxicity, superoxide production, phagocytosis, and protein synthesis. Thus, arginine concentrations similar to those found in sites of inflammation can augment macrophage functions, while those found in plasma (approximately 0.1 mM) and in commonly used culture media (0.4 to 1.2 mM) are inhibitory. Culture in homoarginine, but not D-arginine, ornithine, citrulline, urea, histidine, or lysine also inhibited macrophage tumor cytotoxicity, indicating the specificity of the effect. In contrast to resident macrophages, the tumor cytotoxicity of peritoneal macrophages obtained after C. parvum injection was suppressed by culture in arginine-deficient media. However, L-arginine-deficient media enhanced all other activation-associated functions in C. parvum-elicited macrophages as in resident cells. Arginine-free wound fluid promoted resident macrophage tumoricidal activity when compared with rat serum, and again, the addition of L-arginine was inhibitory. The marked effects of L-arginine availability on macrophage functions, together with the knowledge that these cells modify the extracellular arginine concentration in sites of inflammation through arginase, provide evidence for an autoregulatory mechanism of macrophage activation.
炎症部位，如伤口和某些肿瘤，有显著的巨噬细胞浸润，且精氨酸严重缺乏。研究了精氨酸可用性对巨噬细胞生理功能的影响。当在含有低于0.1 mM L-精氨酸的培养基中培养时，大鼠腹腔常驻巨噬细胞表现出更强的铺展、肿瘤细胞毒性、超氧化物生成、吞噬作用和蛋白质合成。因此，与炎症部位相似的精氨酸浓度可增强巨噬细胞功能，而血浆中（约0.1 mM）和常用培养基中（0.4至1.2 mM）的精氨酸浓度则具有抑制作用。在高精氨酸而非D-精氨酸、鸟氨酸、瓜氨酸、尿素、组氨酸或赖氨酸中培养也会抑制巨噬细胞肿瘤细胞毒性，表明该效应具有特异性。与常驻巨噬细胞不同，微小隐孢子虫注射后获得的腹腔巨噬细胞在精氨酸缺乏的培养基中培养时，其肿瘤细胞毒性受到抑制。然而，与常驻细胞一样，精氨酸缺乏的培养基增强了微小隐孢子虫诱导的巨噬细胞中所有其他与激活相关的功能。与大鼠血清相比，无精氨酸的伤口渗出液促进了常驻巨噬细胞的杀肿瘤活性，同样，添加L-精氨酸具有抑制作用。L-精氨酸可用性对巨噬细胞功能的显著影响，以及这些细胞通过精氨酸酶改变炎症部位细胞外精氨酸浓度的知识，为巨噬细胞激活的自动调节机制提供了证据。
