Djeraba Aouatef, Musset Eugène, van Rooijen Nico, Quéré Pascale
Institut National de la Recherche Agronomique, Station de Pathologie Aviaire et de Parasitologie, 37380 Nouzilly, France.
Vet Microbiol. 2002 May 1;86(3):229-44. doi: 10.1016/s0378-1135(02)00010-x.
The metabolic NO pathway, catalyzed by the enzyme NO synthase in macrophages, is a key defense element against viruses and tumors. However, arginase is an other enzyme able to metabolize the substrate L-arginine, and the two enzymes are alternatively regulated by Th1 and Th2 cytokines in murine macrophages. Marek's disease is characterized by strong immunosuppression and development of T-cell lymphomas in chickens. Inoculation of the very virulent strain of MDV RB-1B induced strong and long-lasting arginase macrophage-dependent activity, which was inhibited by L-norvaline in vitro, but induced low NO production in monocytes and splenocytes from highly susceptible B(13)/B(13) chickens. By contrast, in B(21)/B(21) chickens genetically resistant to tumor development, RB-1B induced a weak and transient increase in arginase activity and strong NO production. The vaccinal HVT strain did not induce any arginase activity in monocytes or splenocytes. Moreover, vaccination with HVT prevented tumor appearance after RB-1B challenge and increase in arginase activity, but favored NO production in susceptible chickens. Differential expression of NO synthase and arginase was modulated in chicken macrophages, with IFN-gamma and LPS being strong inducers of both, depending on the type of macrophage, and TGF-beta 1 and PGE(2) stimulating only arginase activity. This increase in arginase activity in macrophages from chickens inoculated with Marek's disease virus might thus be due to a direct effect of the virus on macrophages, possibly through viral products, or to indirect effects on the cytokine balance.
由巨噬细胞中的一氧化氮合酶催化的代谢性一氧化氮途径是抵御病毒和肿瘤的关键防御要素。然而，精氨酸酶是另一种能够代谢底物L-精氨酸的酶，在小鼠巨噬细胞中，这两种酶受Th1和Th2细胞因子的交替调控。马立克氏病的特征是鸡出现强烈的免疫抑制和T细胞淋巴瘤。接种MDV RB-1B的超强毒株可诱导强烈且持久的精氨酸酶巨噬细胞依赖性活性，体外实验中L-正缬氨酸可抑制该活性，但在高度易感的B(13)/B(13)鸡的单核细胞和脾细胞中诱导产生的一氧化氮水平较低。相比之下，在对肿瘤发展具有遗传抗性的B(21)/B(21)鸡中，RB-1B诱导精氨酸酶活性出现微弱且短暂的增加以及强烈的一氧化氮产生。疫苗株HVT在单核细胞或脾细胞中未诱导任何精氨酸酶活性。此外，用HVT疫苗接种可预防RB-1B攻击后肿瘤的出现以及精氨酸酶活性的增加，但有利于易感鸡产生一氧化氮。一氧化氮合酶和精氨酸酶的差异表达在鸡巨噬细胞中受到调控，干扰素-γ和脂多糖是两者的强诱导剂，具体取决于巨噬细胞的类型，而转化生长因子-β1和前列腺素E2仅刺激精氨酸酶活性。因此，接种马立克氏病病毒的鸡巨噬细胞中精氨酸酶活性的增加可能是由于病毒对巨噬细胞的直接作用，可能是通过病毒产物，也可能是对细胞因子平衡的间接影响。
