Lewandowicz Anna M, Pawliczak Rafał
Zakład Immunopatologii Katedry Immunologii, Wydział Kształcenia Podyplomowego Uniwersytetu Medycznego w Łodzi, Łodz, Poland.
Postepy Hig Med Dosw (Online). 2007;61:156-66.
Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. Airway inflammation is associated with an enhanced expression of inducible nitric oxide synthase. This increases nitric oxide production and results in higher levels of NO* gas in exhaled air. Measurement of exhaled nitric oxide is a very useful non-invasive method in the diagnosis and treatment monitoring of asthma. However, the role of nitric oxide in asthma, still under intense debate, should not be regarded only as a consequence of its abundance, but rather as an impairment of the mechanisms that regulate its synthesis and activity, including reducing nitric oxide production by neuronal and endothelial synthase. Arginine is a substrate for both nitric oxide synthase and arginase. Arginase expression in the lung is strongly induced by cytokines, in particular IL-4 and IL-13, which are produced at elevated level in asthmatic airways and which activate inflammatory pathways. Arginase modulates nitric oxide synthase activity and provides a precursor for polyamines (putrescine, spermidine, and spermine) and proline, which stimulate cell growth and collagen synthesis, respectively. Therefore, arginase might also be involved in inflammation-induced airway remodeling in chronic asthma. This review presents arginine homeostasis in asthma and focuses not only on inducible nitric oxide synthase, but also on impairment of constitutive nitric oxide synthase activity and the overproduction of arginase downstream products.
哮喘是一种气道慢性炎症性疾病，其中许多细胞和细胞成分都发挥着作用。气道炎症与诱导型一氧化氮合酶的表达增强有关。这会增加一氧化氮的产生，并导致呼出气体中一氧化氮（NO*）水平升高。呼出一氧化氮的测量是哮喘诊断和治疗监测中一种非常有用的非侵入性方法。然而，一氧化氮在哮喘中的作用仍在激烈争论中，不应仅将其视为一氧化氮含量丰富的结果，而应视为调节其合成和活性的机制受损，包括神经元型和内皮型合酶减少一氧化氮的产生。精氨酸是一氧化氮合酶和精氨酸酶的底物。肺中精氨酸酶的表达受到细胞因子，特别是白细胞介素-4和白细胞介素-13的强烈诱导，这些细胞因子在哮喘气道中水平升高，并激活炎症途径。精氨酸酶调节一氧化氮合酶的活性，并为多胺（腐胺、亚精胺和精胺）和脯氨酸提供前体，它们分别刺激细胞生长和胶原蛋白合成。因此，精氨酸酶也可能参与慢性哮喘中炎症诱导的气道重塑。这篇综述介绍了哮喘中的精氨酸稳态，不仅关注诱导型一氧化氮合酶，还关注组成型一氧化氮合酶活性受损以及精氨酸酶下游产物的过量产生。
