Adp-ribosylation Cycles

ADP-核糖化是在一系列细菌毒素和哺乳动物酶的催化下，将NAD的ADP-核糖部分转移到靶蛋白上。一些毒素转移酶似乎与细菌引起的疾病有关。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。其他哺乳动物转移酶有待分泌。在实验室中已经克隆了一个哺乳动物酶家族。值得注意的是，这些酶在参与炎症反应的细胞中特异表达。免疫细胞表面存在NAD代谢酶(例如，ADP-核糖基转移酶(ART)1)，这表明在炎症和细胞溶解部位NAD或其代谢产物具有潜在的免疫调节活性，其中细胞外NAD水平可能较高。在人类呼吸道中，管腔内的上皮细胞和管腔内的细胞(例如，多形核细胞)参与先天免疫反应，并在其表面分泌或具有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，这导致了ADP核糖基化可以改变其生物学活性的假说。研究小组发现，ART-1可以修饰α-防御素-1的精氨酸-14。ADP-核糖化防御素-1降低了A549细胞的细胞毒活性和抗菌活性，但仍能刺激T细胞趋化和IL-8的释放。此外，ADP核糖化防御素抑制了未经修饰的防御素-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，而在不吸烟者中没有发现，证实了它在体内的存在。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，也许还有其他阳离子分子，改变其生物学特性，在先天性免疫反应中发挥重要的调节作用。这些数据表明，ADP-核糖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.