J. Cantor, J. Cantor, Bronislava Shteyngart, J. Cerreta, Ming Liu, G. Armand, G. Turino
{"title":"透明质酸对体外弹性纤维损伤和体内弹性酶诱导的空气空间扩大的影响。","authors":"J. Cantor, J. Cantor, Bronislava Shteyngart, J. Cerreta, Ming Liu, G. Armand, G. Turino","doi":"10.1111/J.1525-1373.2000.22508.X","DOIUrl":null,"url":null,"abstract":"This laboratory has previously described a method of preventing air-space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA). Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers. In the current study, cell-free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight ( approximately 100 kDa) streptococcal HA to prevent elastolysis. Coating the matrices with HA significantly decreased elastolysis (P<0.05) induced by porcine pancreatic elastase (43%), human neutrophil elastase (53%), and human macrophage metalloelastase (80%). Concomitant in vivo studies examined the ability of an aerosol preparation of the streptococcal HA to prevent experimental emphysema induced by intratracheal administration of porcine pancreatic elastase. As seen with earlier studies involving bovine tracheal HA, a single aerosol exposure significantly decreased elastase-induced airspace enlargement, as measured by the mean linear intercept (107.5 vs 89.6 microm; P < 0. 05). Furthermore, repeated exposure to the HA aerosol for 1 month did not reveal any morphological changes in the lung. The results provide further evidence that aerosolized HA may be an effective means of preventing pulmonary emphysema and perhaps other lung diseases that involve elastic fiber injury.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"28 8 1","pages":"65-71"},"PeriodicalIF":0.0000,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"62","resultStr":"{\"title\":\"The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo.\",\"authors\":\"J. Cantor, J. Cantor, Bronislava Shteyngart, J. Cerreta, Ming Liu, G. Armand, G. Turino\",\"doi\":\"10.1111/J.1525-1373.2000.22508.X\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"This laboratory has previously described a method of preventing air-space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA). Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers. In the current study, cell-free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight ( approximately 100 kDa) streptococcal HA to prevent elastolysis. Coating the matrices with HA significantly decreased elastolysis (P<0.05) induced by porcine pancreatic elastase (43%), human neutrophil elastase (53%), and human macrophage metalloelastase (80%). Concomitant in vivo studies examined the ability of an aerosol preparation of the streptococcal HA to prevent experimental emphysema induced by intratracheal administration of porcine pancreatic elastase. As seen with earlier studies involving bovine tracheal HA, a single aerosol exposure significantly decreased elastase-induced airspace enlargement, as measured by the mean linear intercept (107.5 vs 89.6 microm; P < 0. 05). Furthermore, repeated exposure to the HA aerosol for 1 month did not reveal any morphological changes in the lung. The results provide further evidence that aerosolized HA may be an effective means of preventing pulmonary emphysema and perhaps other lung diseases that involve elastic fiber injury.\",\"PeriodicalId\":20618,\"journal\":{\"name\":\"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine\",\"volume\":\"28 8 1\",\"pages\":\"65-71\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2000-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"62\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/J.1525-1373.2000.22508.X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/J.1525-1373.2000.22508.X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 62
摘要
该实验室先前描述了一种使用雾化透明质酸(HA)防止实验性肺气肿中空气空间扩大的方法。虽然发现透明质酸优先与弹性纤维结合(在肺气肿中,弹性纤维会被弹性蛋白酶分解),但仍有待证明这种附着实际上可以防止纤维受损。在目前的研究中,来自大鼠胸膜间皮细胞的无细胞放射性标记细胞外基质被用于测试低分子量(约100 kDa)链球菌HA防止弹性分解的能力。涂膜透明质酸可显著降低猪胰腺弹性酶(43%)、人中性粒细胞弹性酶(53%)和人巨噬细胞金属弹性酶(80%)诱导的弹性溶解(P<0.05)。同时进行的体内研究检测了链球菌透明质酸的气溶胶制剂预防猪胰腺弹性酶气管内注射引起的实验性肺气肿的能力。正如早期涉及牛气管HA的研究所见,通过平均线性截距(107.5 vs 89.6微米)测量,单次气溶胶暴露显著减少弹性酶引起的空域扩大;P < 0。05). 此外,反复暴露于HA气雾剂1个月未发现肺的任何形态学变化。结果进一步证明,雾化透明质酸可能是预防肺气肿和其他涉及弹性纤维损伤的肺部疾病的有效手段。
The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo.
This laboratory has previously described a method of preventing air-space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA). Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers. In the current study, cell-free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight ( approximately 100 kDa) streptococcal HA to prevent elastolysis. Coating the matrices with HA significantly decreased elastolysis (P<0.05) induced by porcine pancreatic elastase (43%), human neutrophil elastase (53%), and human macrophage metalloelastase (80%). Concomitant in vivo studies examined the ability of an aerosol preparation of the streptococcal HA to prevent experimental emphysema induced by intratracheal administration of porcine pancreatic elastase. As seen with earlier studies involving bovine tracheal HA, a single aerosol exposure significantly decreased elastase-induced airspace enlargement, as measured by the mean linear intercept (107.5 vs 89.6 microm; P < 0. 05). Furthermore, repeated exposure to the HA aerosol for 1 month did not reveal any morphological changes in the lung. The results provide further evidence that aerosolized HA may be an effective means of preventing pulmonary emphysema and perhaps other lung diseases that involve elastic fiber injury.