Döring G
Department of General Hygiene and Environmental Hygiene, Hygiene-Institute, University of Tübingen, Germany.
Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 2):S114-7. doi: 10.1164/ajrccm/150.6_Pt_2.S114.
Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, alpha 1-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.
中性粒细胞被动释放或主动分泌的弹性蛋白酶与多种炎症性疾病的病理过程有关，包括特发性肺纤维化、类风湿性关节炎、成人呼吸窘迫综合征和囊性纤维化。这种丝氨酸蛋白酶具有广泛的底物特异性，可能会攻击中性粒细胞外的许多宿主蛋白，包括肺弹性蛋白和纤连蛋白。这种蛋白水解作用可能会改变正常的周围组织以及炎症灶的蛋白质模式。此外，它在微量时可作为一种强效促分泌素。在慢性炎症期间，中性粒细胞弹性蛋白酶在中性粒细胞外大量存在，而中性粒细胞弹性蛋白酶的主要内源性丝氨酸蛋白酶抑制剂α1-蛋白酶抑制剂很容易被蛋白水解和氧化攻击失活，其原因尚不清楚。释放的中性粒细胞弹性蛋白酶也可能参与调节慢性炎症。在一种反馈机制中，中性粒细胞弹性蛋白酶通过裂解中性粒细胞上的免疫球蛋白、补体成分和1型补体受体来抑制中性粒细胞的刺激以及随之而来的弹性蛋白酶释放。除了中性粒细胞弹性蛋白酶在炎症中的许多有害作用外，后一种机制虽然会严重损害吞噬作用，但鉴于囊性纤维化患者肺部存在持续的细菌病原体，可能尤其有益。
