Segura-Valdez L, Pardo A, Gaxiola M, Uhal B D, Becerril C, Selman M
Instituto Nacional de Enfermedades Respiratorias (Drs. Segura-Valdez, Gaxiola, Selman, and Ms. Becerril), Mexico City, Mexico.
Chest. 2000 Mar;117(3):684-94. doi: 10.1378/chest.117.3.684.
A central feature in the pathogenesis of COPD is the inflammation coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controversial.
We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (MMP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tissues of 10 COPD patients and 5 control subjects. In addition, gelatinase-A and gelatinase-B activities were assessed in BAL obtained from eight COPD patients, and from six healthy nonsmokers and six healthy smoker control subjects.
Tertiary referral center and university laboratories of biochemistry, and lung cell kinetics.
Immunohistochemical analysis of COPD lungs showed a markedly increased expression of collagenases 1 and 2, and gelatinases A and B, while collagenase 3 was not found. Neutrophils exhibited a positive signal for collagenase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were revealed mainly in macrophages and epithelial cells. BAL gelatin zymography showed a moderate increase of progelatinase-A activity and intense bands corresponding to progelatinase B. In situ end labeling of fragmented DNA displayed foci of positive endothelial cells, although some alveolar epithelial, interstitial, and inflammatory cells also revealed intranuclear staining.
These findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.
慢性阻塞性肺疾病（COPD）发病机制的一个核心特征是炎症与异常的蛋白酶/抗蛋白酶平衡并存。然而，不同丝氨酸蛋白酶和金属蛋白酶的可能作用仍存在争议。
我们检测了10例COPD患者和5例对照受试者肺组织中明胶酶A和B（基质金属蛋白酶[MMP]-2和MMP-9）、胶原酶1、2和3（MMP-1、MMP-8和MMP-13）的表达以及细胞凋亡情况。此外，还评估了8例COPD患者、6例健康非吸烟者和6例健康吸烟者对照受试者支气管肺泡灌洗液（BAL）中的明胶酶A和明胶酶B活性。
三级转诊中心以及大学的生物化学和肺细胞动力学实验室。
COPD肺组织的免疫组化分析显示，胶原酶1和2以及明胶酶A和B的表达显著增加，而未发现胶原酶3。中性粒细胞对胶原酶2和明胶酶B呈阳性信号，而胶原酶1和明胶酶A主要在巨噬细胞和上皮细胞中表达。BAL明胶酶谱显示前明胶酶A活性适度增加，对应前明胶酶B的条带较深。DNA片段原位末端标记显示内皮细胞有阳性染色灶，尽管一些肺泡上皮细胞、间质细胞和炎症细胞也有核内染色。
这些发现表明，胶原酶1和2以及明胶酶A和B上调，内皮细胞和上皮细胞死亡增加，这可能通过气道和肺泡结构重塑促进COPD的发病机制。
