Therapeutic application of PEG-DAO in chronic granulomatous disease

我们发现DAO在体外通过与髓过氧化物酶协同作用产生过氧化氢或次卤酸而显示杀菌活性。此外，DAO活性缺陷小鼠显示出对金黄色葡萄球菌感染的易感性增加。我们进一步研究了DAO在慢性肉芽肿病（CGD）中的可能应用，该疾病是由过氧化氢产生的损失引起的。为此，我们开发了聚乙二醇化DAO，其通过增强的渗透性和保留（EPR）效应而不损失酶活性，具有朝向感染部位或炎症部位的方向性。PEG-DAO对CGD中性粒细胞的杀菌作用可恢复，而对髓过氧化物酶的抑制作用可使其消失。因此，DAO是体内产生过氧化氢的抗菌酶之一。此外，通过PEG-DAO补充其可恢复CGD中性粒细胞的杀菌活性。

We found that DAO shows bactericidal activity through hydrogen peroxide or hypohalous acid produced by coordinative function with myeloperoxidase in vitro. Furthermore DAO activity deficient mouse showed increased susceptibility of infection against staphylococcus aureus. We further investigated the possible application of DAO for chronic granulomatous disease (CGD) which is caused by loss of hydrogen peroxide production. For this purpose, we developed pegylated DAO, which has directionality toward infection site or inflammatory site by enhanced permeability and retention (EPR) effect without loss of enzymatic acitivity. Treatment of PEG-DAO to CGD neutrophils recovered its bactericidal function, and abolished by inhibition of myeloperoxidase. In conclusion DAO is one of the antibacterial enzyme in our body by producing the hydrogen peroxide. Furthermore its supplementation by PEG-DAO will may recover the bactericidal acitivty of CGD neutrophils.