Ninomiya H, Ichikawa Y, Koga H, Yano T, Oizumi K
First Department of Internal Medicine, Kurume University, Japan.
Kansenshogaku Zasshi. 1991 Jun;65(6):672-80. doi: 10.11150/kansenshogakuzasshi1970.65.672.
The clinical and pathological features of diffuse panbronchiolitis (DPB) have been well reported to date though its pathogenesis remains unknown. This study was designed to evaluate the protease antiprotease imbalance in patients with DPB. For this purpose, we performed bronchoalveolar lavage (BAL) in sixteen patients with DPB, twelve patients with chronic bronchitis (CB) and control subjects (nine smokers and eleven non-smokers), and determined elastase activity and alpha 1 antitrypsin (alpha 1 AT) concentration in bronchoalveolar lavage fluid (BALF). Elastase activity was measured using a synthetic substrate, succinyl-tri-L-alanine-p-nitroanilide. BALF from eleven of sixteen patients with DPB showed elastase activity. However, only two of twelve patients with CB showed elastase activity, and control subjects did not show any elastase activity in BALF. Although alpha 1 AT concentration is elevated in BALF from patients with DPB, it is assumed that elastase burden exceeded the elastase inhibitory capacity of alpha 1 AT in BALF. The percentage of neutrophils in BALF correlated significantly with elastase activity which was inhibited by DFP, but not by EDTA. These data revealed that the elastase in BALF was a serine protease of neutrophil origin. In five DPB-patients treated with low-dose long-term erythromycin chemotherapy, elastase activity in BALF decreased significantly. The above mentioned findings suggest that the neutrophil elastase plays an important role in the pathogenesis of DPB, and the mode of action of erythromycin on DPB is to decrease the elastase burden.
尽管弥漫性泛细支气管炎（DPB）的发病机制尚不清楚，但迄今为止其临床和病理特征已有详尽报道。本研究旨在评估DPB患者体内蛋白酶 - 抗蛋白酶失衡情况。为此，我们对16例DPB患者、12例慢性支气管炎（CB）患者及对照者（9名吸烟者和11名非吸烟者）进行了支气管肺泡灌洗（BAL），并测定了支气管肺泡灌洗液（BALF）中的弹性蛋白酶活性和α1抗胰蛋白酶（α1AT）浓度。弹性蛋白酶活性采用合成底物琥珀酰 - 三 - L - 丙氨酸 - 对硝基苯胺进行测定。16例DPB患者中有11例的BALF显示出弹性蛋白酶活性。然而，12例CB患者中只有2例的BALF显示出弹性蛋白酶活性，对照者的BALF未显示任何弹性蛋白酶活性。尽管DPB患者BALF中的α1AT浓度升高，但推测BALF中弹性蛋白酶负荷超过了α1AT的弹性蛋白酶抑制能力。BALF中中性粒细胞百分比与被二异丙基氟磷酸（DFP）而非乙二胺四乙酸（EDTA）抑制的弹性蛋白酶活性显著相关。这些数据表明BALF中的弹性蛋白酶是源自中性粒细胞的丝氨酸蛋白酶。在5例接受低剂量长期红霉素化疗的DPB患者中，BALF中的弹性蛋白酶活性显著降低。上述发现提示中性粒细胞弹性蛋白酶在DPB发病机制中起重要作用，红霉素对DPB的作用方式是减轻弹性蛋白酶负荷。
