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The role of secretory leukocyte proteinase inhibitor and elafin (elastase-specific inhibitor/skin-derived antileukoprotease) as alarm antiproteinases in inflammatory lung disease

机译:分泌性白细胞蛋白酶抑制剂和弹性蛋白(弹性蛋白酶特异性抑制剂/皮肤抗白蛋白)在炎症性肺疾病中作为警报抗蛋白酶的作用

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摘要

Secretory leukocyte proteinase inhibitor and elafin are two low-molecular-mass elastase inhibitors that are mainly synthesized locally at mucosal sites. It is thought that their physicochemical properties allow them to efficiently inhibit target enzymes, such as neutrophil elastase, released into the interstitium. Historically, in the lung, these inhibitors were first purified from secretions of patients with chronic obstructive pulmonary disease and cystic fibrosis. This suggested that they might be important in controlling excessive neutrophil elastase release in these pathologies. They are upregulated by 'alarm signals' such as bacterial lipopolysaccharides, and cytokines such as interleukin-1 and tumor necrosis factor and have been shown to be active against Gram-positive and Gram-negative bacteria, so that they have joined the growing list of antimicrobial 'defensin-like' peptides produced by the lung. Their site of synthesis and presumed functions make them very attractive candidates as potential therapeutic agents under conditions in which the excessive release of elastase by neutrophils might be detrimental. Because of its natural tropism for the lung, the use of adenovirus-mediated gene transfer is extremely promising in such applications.
机译:分泌型白细胞蛋白酶抑制剂和弹性蛋白是两种低分子质量弹性蛋白酶抑制剂,主要在粘膜部位局部合成。据认为,它们的理化性质使它们能够有效抑制释放到间质中的靶酶,例如嗜中性粒细胞弹性蛋白酶。历史上,在肺中,首先从患有慢性阻塞性肺疾病和囊性纤维化的患者的分泌物中纯化这些抑制剂。这表明它们在控制这些病理中嗜中性粒细胞弹性蛋白酶的过量释放中可能很重要。它们被细菌脂质多糖等“警报信号”和白介素-1和肿瘤坏死因子等细胞因子上调,并已被证明对革兰氏阳性和革兰氏阴性细菌具有活性,因此它们已加入肺产生的抗菌“防御素样”肽。它们的合成位点和推测的功能使它们在中性粒细胞过度释放弹性蛋白酶可能有害的条件下,成为潜在治疗剂的极具吸引力的候选者。由于其对肺的天然嗜性,在此类应用中使用腺病毒介导的基因转移极为有前途。

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