Matrix metalloproteinase expression and production by alveolar macrophages in emphysema
Matrix metalloproteinase expression and production by alveolar macrophages in emphysema
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DOI：
10.1164/ajrccm.156.1.9612018
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发表时间：
1997-07-01
影响因子：
24.7
通讯作者：
OConnor, CM
中科院分区：
文献类型：
--
作者：
Finlay, GA;ODriscoll, LR;OConnor, CM
这项研究的目的是检验肺泡巨噬细胞是肺气肿肺中基质降解蛋白水解酶的重要来源的假设。10例肺气肿患者和10例健康志愿者的肺泡灌洗液中巨噬细胞体外培养24小时，半定量检测基质金属蛋白酶(MMPs)、明胶酶A和B、巨噬细胞金属弹性酶(MME)和间质胶原酶的mRNA转录水平。将这些MMPs释放到培养上清液中，并分泌中性粒细胞弹力素样活性。在肺气肿患者的巨噬细胞中观察到明胶酶B(p<；0.0005)和间质胶原酶(p<；0.0005)的转录水平升高。在患者巨噬细胞的条件培养液中也检测到胶原酶的增加(P<；0.001)和中性粒细胞的弹力样活性(P<；0.001)。在明胶酶B中，复杂形式的酶由患者分泌，但不由对照巨噬细胞分泌。明胶酶A或MME的转录水平在患者和对照组之间没有观察到差异，在两组的巨噬细胞条件培养液中都没有检测到这两种酶。这些结果直接证明肺气肿肺泡巨噬细胞产生大量具有弹性和胶原蛋白分解活性的基质降解酶。
The aim of this study was to examine the hypothesis that alveolar macrophages represent a significant source of matrix-degrading proteinases in the emphysematous lung. Macrophages from bronchoalveolar lavage fluid of 10 patients with emphysema and 10 normal volunteers were maintained in vitro for 24 h and assessed semiquantitatively for mRNA transcript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase. Release of these MMPs into the culture medium and secretion of neutrophil elastaselike activity was also assessed. Elevated levels of mRNA transcripts for gelatinase B (p < 0.0005) and interstitial collagenase (p < 0.0005) were observed in macrophages from emphysematous patients. Increased collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were also measured in conditioned medium from patient macrophages. With gelatinase B, complexed forms of the enzyme were secreted by patient but not by control macrophages. No difference in transcript levels of gelatinase A or MME was observed between patient and control samples, and neither enzyme was detected in macrophage-conditioned media from either group. These results directly demonstrate that alveolar macrophages from the emphysematous lung produce elevated quantities of matrix-degrading enzymes with both elastolytic and collagenolytic activities.