Pardo A, Selman M, Ridge K, Barrios R, Sznajder J I
Facultad de Ciencias, UNAM, Coyoacán, Mexico.
Am J Respir Crit Care Med. 1996 Oct;154(4 Pt 1):1067-75. doi: 10.1164/ajrccm.154.4.8887609.
Exposure of adult rats to 100% O2 produces a lethal injury by 72 h. We reasoned that matrix metalloproteinases participate in the pathogenesis of hyperoxic lung injury. To that end we studied the expression and activity of gelatinases A and B and interstitial collagenase in lung tissues and bronchoalveolar lavage fluids (BALF) of rats exposed to 100% oxygen for 60 h. Gelatin zymography of BALF samples revealed a 472 kDa molecular species both in controls and oxygen-exposed animals. In addition, BALF from hyperoxic rats exhibited a 95-kDa gelatinase. Likewise, BALF total gelatinolytic and collagenolytic activities were significantly increased in oxygen-exposed rats. In situ hybridization revealed an increase in type IV collagenases as well as interstitial collagenase mRNAs in the oxygen-exposed lungs. The three enzymes were expressed by alveolar macrophages, and in variable degrees by interstitial and alveolar epithelial cells. Immunoreactive gelatinase B and collagenase paralleled the cell localization of the mRNAs but were also detected in the alveolar walls and interstitium. In situ zymography showed gelatinolytic activity in frozen sections of oxygen-exposed lungs but not in normal lungs. The upregulation of these metalloproteinases during acute exposure to 100% O2 suggests that they might contribute to hyperoxic lung damage through the degradation of extracellular matrix components.
成年大鼠暴露于100%氧气中72小时会产生致命损伤。我们推测基质金属蛋白酶参与了高氧性肺损伤的发病机制。为此，我们研究了暴露于100%氧气60小时的大鼠肺组织和支气管肺泡灌洗液（BALF）中明胶酶A、B和间质胶原酶的表达及活性。BALF样本的明胶酶谱分析显示，对照组和氧气暴露组动物中均存在一种472 kDa的分子种类。此外，高氧大鼠的BALF中出现了一种95 kDa的明胶酶。同样，氧气暴露组大鼠的BALF总明胶水解和胶原水解活性显著增加。原位杂交显示，氧气暴露肺组织中IV型胶原酶以及间质胶原酶的mRNA水平升高。这三种酶在肺泡巨噬细胞中表达，在间质和肺泡上皮细胞中也有不同程度的表达。免疫反应性明胶酶B和胶原酶与mRNA的细胞定位一致，但在肺泡壁和间质中也能检测到。原位酶谱分析显示，氧气暴露肺组织的冰冻切片中有明胶水解活性，而正常肺组织中没有。急性暴露于100%氧气期间这些金属蛋白酶的上调表明，它们可能通过降解细胞外基质成分而导致高氧性肺损伤。
