Vered M, Simon S, Dearing R, Janoff A
Department of Pathology, State University of New York, Stony Brook 11794.
Exp Lung Res. 1988;14(1):67-83. doi: 10.3109/01902148809062851.
We previously demonstrated that pneumococcal extracts contain a highly specific inhibitor of human neutrophil elastase (HNE). We now show that the active inhibitor in these extracts is a high-molecular-weight, heat-stable substance that appears to be RNA, since inhibitory activity of pneumococcal extracts is decreased by incubation with ribonuclease but not by incubation with deoxyribonuclease or proteinase K. Moreover, metabolically labeled ([3H]uridine) pneumococcal RNA, isolated by phenol extraction followed by ethanol precipitation, strongly inhibits HNE. Pneumococcal capsular polysaccharide, although polyanionic, is only weakly inhibitory toward HNE and is not a major source of elastase-inhibitory activity in pneumococcal extracts. On the other hand, the capsule of Haemophilus influenzae type b contains polyribosylribitol phosphate. This highly charged polyanion possesses HNE-inhibitory activity, but only under special circumstances to be discussed below. Pneumococci (type I, type II smooth, type II rough) and H. influenzae (type b) all release HNE-inhibitory activity into their culture medium during growth. By contrast, Klebsiella pneumoniae and Staphylococcus aureus release little (if any) stable HNE-inhibitory activity during growth. We propose that some bacterial pneumonias may spare host tissue because polyanions released by the invading microorganisms (e.g. RNA from autolysing pneumococci) inhibit elastase released from inflammatory neutrophils and thereby modulate accompanying tissue proteolysis. Pneumonias caused by microorganisms that do not release stable polyanionic inhibitors of HNE (e.g., Staphylococcus and Klebsiella) may be correspondingly more injurious to the lung.
我们先前证明肺炎球菌提取物含有一种人中性粒细胞弹性蛋白酶（HNE）的高度特异性抑制剂。我们现在表明，这些提取物中的活性抑制剂是一种高分子量、热稳定的物质，似乎是RNA，因为肺炎球菌提取物与核糖核酸酶孵育后抑制活性降低，而与脱氧核糖核酸酶或蛋白酶K孵育后抑制活性未降低。此外，通过苯酚提取然后乙醇沉淀分离的经代谢标记（[3H]尿苷）的肺炎球菌RNA强烈抑制HNE。肺炎球菌荚膜多糖虽然是聚阴离子，但对HNE的抑制作用较弱，不是肺炎球菌提取物中弹性蛋白酶抑制活性的主要来源。另一方面，b型流感嗜血杆菌的荚膜含有聚核糖基核糖醇磷酸。这种高电荷的聚阴离子具有HNE抑制活性，但仅在以下将讨论的特殊情况下。肺炎球菌（I型、II型光滑型、II型粗糙型）和b型流感嗜血杆菌在生长过程中都会将HNE抑制活性释放到培养基中。相比之下，肺炎克雷伯菌和金黄色葡萄球菌在生长过程中释放的稳定HNE抑制活性很少（如果有的话）。我们提出，一些细菌性肺炎可能会使宿主组织免受损伤，因为入侵微生物释放的聚阴离子（例如自溶肺炎球菌的RNA）抑制炎症中性粒细胞释放的弹性蛋白酶，从而调节伴随的组织蛋白水解。由不释放HNE稳定聚阴离子抑制剂的微生物（例如葡萄球菌和克雷伯菌）引起的肺炎可能相应地对肺部造成更大的损伤。
