Lungarella Giuseppe, Cavarra Eleonora, Lucattelli Monica, Martorana Piero A
Department of Physiopathology and Experimental Medicine, University of Siena, via Aldo Moro n.6, I-53100 Siena, Italy.
Int J Biochem Cell Biol. 2008;40(6-7):1287-96. doi: 10.1016/j.biocel.2007.12.008. Epub 2007 Dec 24.
The purpose of this review was to modify the prevailing view that neutrophil elastase (NE) is mainly a matrix-degrading enzyme. Recent observations indicate that the role of NE in inflammation is more complex than the simple degradation of extra-cellular matrix components. Several lines of evidence suggest that NE aims specifically at a variety of regulatory functions in local inflammatory processes. This enzyme can modulate many biological functions by promoting chemokine and cytokine activation and degradation, cytokine receptor shedding, proteolysis of cytokine binding proteins and the activation of different specific cell surface receptors. However, the current knowledge of regulatory mechanisms by which NE potentially regulates inflammatory processes is primarily derived from in vitro studies. The extent of these NE-dependent pathways and their relevance under various pathophysiological conditions remains poorly understood and a matter for further investigation. Recent studies suggest that NE not only plays a key role in lung destruction (emphysema) but can also modulate proliferative changes (fibrosis) in inflammatory processes. Thus, NE could be considered to have potential multiple roles in the pathogenesis of both emphysema and lung fibrosis.
本综述的目的是修正目前普遍认为中性粒细胞弹性蛋白酶（NE）主要是一种基质降解酶的观点。最近的观察结果表明，NE在炎症中的作用比单纯降解细胞外基质成分更为复杂。有几条证据表明，NE专门针对局部炎症过程中的多种调节功能。这种酶可以通过促进趋化因子和细胞因子的激活与降解、细胞因子受体脱落、细胞因子结合蛋白的蛋白水解以及不同特异性细胞表面受体的激活来调节多种生物学功能。然而，目前关于NE潜在调节炎症过程的机制的认识主要来自体外研究。这些NE依赖途径的程度及其在各种病理生理条件下的相关性仍知之甚少，有待进一步研究。最近的研究表明，NE不仅在肺破坏（肺气肿）中起关键作用，还可以调节炎症过程中的增殖性变化（纤维化）。因此，NE在肺气肿和肺纤维化的发病机制中可能具有多种潜在作用。
