Piccioni P D, Kramps J A, Rudolphus A, Bulgheroni A, Luisetti M
Istituto di Tisiologia e Malattie Respiratorie, IRCCS Policlinico San Matteo, Università di Pavia, Italy.
Chest. 1992 Nov;102(5):1470-6. doi: 10.1378/chest.102.5.1470.
In order to characterize the imbalance between proteinases and proteinase inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr) with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of sputum was used for bacteriologic determinations, and the remainder was centrifuged in order to obtain gel and sol phases. On the basis of the bacteriologic data, patients were divided into colonized patients (14) and noncolonized patients (11). All of the major inhibitors were immunologically detectable in sol phases without a significant difference between colonized and noncolonized patients (alpha 1-proteinase inhibitor [alpha 1-PI], 2.56 microM +/- 0.53 microM and 2.39 microM +/- 0.72 microM; alpha 2-macroglobulin [alpha 2-MG], 0.21 microM +/- 0.07 microM and 0.16 microM +/- 0.05 microM; antileukoprotease (ALP), 1.78 microM +/- 0.57 microM and 1.53 microM +/- 0.6 microM, respectively [mean +/- SE]). With regard to proteinase activities, both free elastase-like and free chymotrypsin-like activities were detectable in the majority of patients (15/25) (0.59 microM +/- 0.15 microM and 0.74 microM +/- 0.15 microM for elastase-like activity [ELA], and 0.010 microM +/- 0.003 microM and 0.017 microM +/- 0.007 microM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The inhibitory profile of proteinase activities, performed by means of a panel of inhibitors, allowed us to assign specific activities mainly to neutrophil elastase and cathepsin G (Cat G). Next we looked at the relationships between inhibitors and proteinase activities. We found a significant negative correlation between neutrophil elastase activity and ALP (r = -0.58; p < 0.01). In confirmation of this suggestion, sol phases were divided into samples (15) with detectable ELA (> 0.50 microM) and samples (10) with no detectable ELA (< 0.18 microM). Levels of alpha 1-PI and alpha 2-MG did not differ significantly between the two groups, whereas ALP values were higher in the group with no detectable ELA (3.12 microM +/- 0.69 microM) than in the other group (0.58 microM +/- 0.21 microM; p < 0.001). We conclude that most sputum sol phases from patients with exacerbated COPD have a high burden of free neutrophil elastase and Cat G. Antileukoprotease seems to be the major naturally occurring inhibitor effective in the modulation of proteinase activities in bronchial secretions under these conditions.
为了描述痰液溶胶相中蛋白酶和蛋白酶抑制剂之间的失衡情况，我们研究了25例慢性阻塞性肺疾病（COPD）急性加重期患者（平均年龄59±11岁）。取一份痰液进行细菌学检测，其余痰液进行离心以获得凝胶相和溶胶相。根据细菌学数据，将患者分为定植患者（14例）和未定植患者（11例）。在溶胶相中可通过免疫方法检测到所有主要抑制剂，定植患者和未定植患者之间无显著差异（α1 - 蛋白酶抑制剂[α1 - PI]，分别为2.56μM±0.53μM和2.39μM±0.72μM；α2 - 巨球蛋白[α2 - MG]，分别为0.21μM±0.07μM和0.16μM±0.05μM；抗白细胞蛋白酶（ALP），分别为1.78μM±0.57μM和1.53μM±0.6μM[均值±标准误]）。关于蛋白酶活性，大多数患者（15/25）可检测到游离弹性蛋白酶样活性和游离糜蛋白酶样活性（弹性蛋白酶样活性[ELA]分别为0.59μM±0.15μM和0.74μM±0.15μM，糜蛋白酶样活性[CLA]分别为0.010μM±0.003μM和0.017μM±0.007μM[均值±标准误]）。通过一组抑制剂对蛋白酶活性进行抑制谱分析，使我们能够将特定活性主要归因于中性粒细胞弹性蛋白酶和组织蛋白酶G（Cat G）。接下来我们研究了抑制剂与蛋白酶活性之间的关系。我们发现中性粒细胞弹性蛋白酶活性与ALP之间存在显著负相关（r = -0.58；p < 0.01）。为证实这一结果，将溶胶相分为可检测到ELA（> 0.50μM）的样本（15份）和未检测到ELA（< 0.18μM）的样本（10份）。两组之间α1 - PI和α2 - MG水平无显著差异，而未检测到ELA的组中ALP值（3.12μM±0.69μM）高于另一组（0.58μM±0.21μM；p < 0.001）。我们得出结论COPD急性加重期患者的大多数痰液溶胶相具有高负荷的游离中性粒细胞弹性蛋白酶和Cat G。在这些情况下，抗白细胞蛋白酶似乎是在调节支气管分泌物中蛋白酶活性方面有效的主要天然存在的抑制剂。
