Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha 1-antiprotease.
Demonstration of a free elastolytic metalloenzyme in human lung lavage fluid and its relationship to alpha 1-antiprotease.
复制标题
演示人肺灌洗液中的游离弹力分解金属酶及其与 α1-抗蛋白酶的关系。
DOI：
10.1164/arrd.1984.129.6.943
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Gee,JB
中科院分区：
文献类型：
--
作者：
Niederman,MS;Fritts,LL;Merrill,WW;Fick,RB;Matthay,RA;Reynolds,HY;Gee,JB
虽然人肺泡巨噬细胞在组织培养可以分泌弹性蛋白酶的金属酶，不被α 1-抗蛋白酶（AAP）灭活，这种蛋白水解活性的水平及其与AAP在人肺灌洗液（HLF）的关系是未知的，从以前的研究。因此，我们测量了15名吸烟者和10名非吸烟者的浓缩（20至30倍）HLF中的弹性蛋白溶解活性，并将结果与这些液体中AAP的测量结果相关。吸烟者对α 14 C弹性蛋白底物的活性（平均值± SEM）（表示为每毫克灌洗液蛋白中猪胰腺弹性蛋白酶当量的纳克数）为18.9 ± 6.7，显著超过（p = 0.05）非吸烟者的水平4.4 ± 1.8。与合成的弹性蛋白样发色团底物琥珀酰-三丙氨酸-硝基苯胺（SLAPN），在个别样品中的活性降低79%，EDTA，金属蛋白酶抑制剂，而活性仅减少了29%，在PMSF，丝氨酸蛋白酶抑制剂的存在下。此外，使用HLF和14 C弹性蛋白底物的混合样品，EDTA消除了80%的对弹性蛋白底物的活性，而PMSF消除了51%。用14 C弹性蛋白底物测得的活性与抗原AAP呈负相关（r =-0.5，p = 0.01），但在该活性与HLF细胞数、细胞活力、分类计数或受试者吸烟史之间未发现相关性。HLF中14 C弹性蛋白的活性检测，主要是金属酶抑制剂的特性，在存在抗原性可检测的AAP的情况下，可能与人类肺气肿的发病相关。
Although the human alveolar macrophage in tissue culture can secrete an elastolytic metalloenzyme that is not inactivated by alpha1-antiprotease (AAP), levels of this proteolytic activity and its relationship to AAP in human lung lavage fluid (HLF) are unknown from previous studies. Therefore, we measured elastolytic activity in concentrated (20- to 30-fold) HLF from 15 smokers and 10 nonsmokers and related results to measurements of AAP in these fluids. Activity (mean ± SEM) against a14C elastin substrate (expressed as nanograms of porcine pancreatic elastase equivalents per milligram of lavage fluid protein) in smokers, 18.9 ± 6.7, significantly exceeded (p = 0.05) levels present in nonsmokers, 4.4 ± 1.8. With the synthetic elastin-like chromophore substrate succinyl-trialanine-nitroanilide (SLAPN), activity in individual samples was reduced 79% by EDTA, a metalloproteinase inhibitor, whereas activity was reduced by only 29% in the presence of PMSF, a serine proteinase inhibitor. In addition, using a pooled sample of HLF and14C elastin substrate, 80% of activity against the elastin substrate was eliminated by EDTA, whereas 51% was eliminated by PMSF. The activity measured with14C elastin substrate correlated inversely with antigenic AAP (r = -0.5, p = 0.01), but no correlations were found between this activity and HLF cell number, cell viability, differential count, or subject smoking history. The detection of activity with14C elastin in HLF, with primarily a metalloenzyme inhibitor profile, in the presence of antigenically detectable AAP, may have pathogenetic relevance for emphysema in humans.