Adp-ribosylation Cycles

在adp核糖基化过程中，NAD的adp核糖部分被转移到目标蛋白上，这是由一系列细菌毒素和哺乳动物酶催化的。一些毒素转移酶似乎是由这种细菌引起的疾病的原因。哺乳动物的酶位于细胞内和细胞表面，有时通过糖基磷脂酰肌醇锚点连接。其他哺乳动物的转移酶似乎也在分泌。哺乳动物酶的一个家族已经在实验室里克隆出来。值得注意的是，这些酶在参与炎症反应的细胞中特异性表达。免疫细胞表面存在NAD代谢酶（如adp -核糖基转移酶（ART）1），表明在细胞外NAD水平较高的炎症和细胞裂解部位，外源性NAD或其代谢物可能具有免疫调节活性。在人气道中，腔内上皮细胞和腔内细胞（如多形核细胞）参与先天免疫反应，分泌或在其表面具有NAD：精氨酸adp -核糖基转移酶。防御素是由免疫细胞分泌的抗菌肽，富含精氨酸，因此adp核糖基化可以改变其生物活性。研究小组发现，ART-1修饰α -防御素-1的精氨酸-14。adp核糖基化的防御素-1降低了A549细胞的细胞毒性和抗菌活性，但仍刺激t细胞趋化性和IL-8的释放。此外，adp核糖基化的防御素抑制未修饰的防御素-1的细胞毒性和抗菌活性。在吸烟者的支气管肺泡灌洗液中发现了adp核糖化防御素-1，但在非吸烟者中没有发现，证实了其在体内的存在。因此，气道NAD：精氨酸adp -核糖基转移酶可能通过修饰α防御素-1和其他阳离子分子，改变其生物学特性，在先天免疫反应中发挥重要的调节作用。这些数据表明，adp核糖基化可能参与调节先天免疫反应。

ADP-ribosylation, in which the ADP-ribose moiety of NAD is transferred to a target protein, is catalyzed by a family of bacterial toxins and mammalian enzymes. Some toxin transferases appear to be responsible for the diseases caused by the bacterium. The mammalian enzymes are located both within the cell and on the cell surface, sometimes, linked through a glycosylphosphatidylinositol anchor. Other mammalian transferases apppear to be secreted. A family of the mammalian enzymes have been cloned in the laboratory. Of note, these enzymes are specifically expressed in cells involved in the inflammatory response.The presence of NAD-metabolizing enzymes (e.g., ADP-ribosyltransferase (ART)1) on the surface of immune cells suggests a potential immunomodulatory activity for ecto-NAD or its metabolites at sites of inflammation and cell lysis where extracellular levels of NAD may be high. In human airways, epithelial cells lining the lumen and intraluminal cells (e.g., polymorphonuclear cells) participate in the innate immune response and secrete or have on their surface NAD:arginine ADP-ribosyltransferases. Defensins, antimicrobial peptides secreted by immune cells, are arginine-rich, leading to the hypothesis that ADP-ribosylation could modify their biological activities. The group found that ART-1 modifies arginine-14 of alpha-defensin-1. ADP-ribosylated defensin-1 had decreased cytotoxic and antimicrobial activities but still stimulated T-cell chemotaxis and IL-8 release from A549 cells. In addition, ADP-ribosylated defensin inhibited the cytotoxic and antimicrobial activities of unmodified defensin-1. ADP-ribosylated defensin-1 was identified in bronchoalveolar lavage fluid from smokers, but not from nonsmokers, confirming its existence in vivo. Thus, airway NAD:arginine ADP-ribosyltransferases could have an important regulatory role in the innate immune response through modification of alpha defensin-1, and perhaps other cationic molecules, with alteration of their biological properties. These data suggest that ADP-ribosylation may be involved in modulating the innate immune response.