Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability
Virulence factors from Pseudomonas aeruginosa increase lung epithelial permeability
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DOI：
10.1007/s004080000031
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发表时间：
2000-09-01
期刊：
影响因子：
5
通讯作者：
Peterson, BT
中科院分区：
文献类型：
--
作者：
Azghani, AO;Miller, EJ;Peterson, BT
铜绿假单胞菌感染经常合并肺损伤，在免疫功能低下或虚弱的人中可能是致命的。我们实验室以前的研究表明，来自铜绿假单胞菌的弹性蛋白酶通过破坏上皮细胞之间的紧密连接来增加上皮细胞的通透性。由于宿主的炎症反应是细菌感染的一个显著特征，我们推测来自这种生物的额外毒力因子可以通过促进中性粒细胞的积累来延长和增加最初的肺损伤。为了验证这一假设，我们比较了豚鼠对来自铜绿假单胞菌的弹性蛋白酶(PE)和脂多糖(LPS)气雾剂的反应。每次治疗后，我们测量上皮通透性和中性粒细胞、白介素8(IL-8)和上皮衬里液体(ELF)中的β-葡萄糖醛酸苷酶的积聚。我们发现PE增加了上皮的通透性，通过测量雾化的放射性标记白蛋白从空气中的清除率和上皮衬里液体中血浆白蛋白的浓度来衡量，但在中性粒细胞重新聚集到肺内方面不如LPS有效。相反，内毒素对ELF上皮细胞无明显影响，但可增加ELF中性粒细胞、IL-8和β-葡萄糖苷酸酶的浓度。PE引起的上皮通透性增加不会引起肺部炎症，但可能促进内毒素诱导的中性粒细胞内流。
Pseudomonas aeruginosa infection frequently complicates lung injury and can be fatal in immunocompromised or debilitated individuals. Previous studies from our laboratory indicate that elastase from P, aeruginosa increases epithelial permeability by disrupting tight junctions between epithelial cells. Because the inflammatory reaction of the host is a prominent feature of bacterial infection, we reasoned that additional virulence factors from this organism could extend and augment the initial pulmonary injury by prompting accumulation of neutrophils. To test this hypothesis, we compared responses of guinea pigs to aerosols of elastase (PE) and lipopolysaccharide (LPS) from P. aeruginosa. After each treatment, we measured epithelial permeability and accumulation of neutrophils, interleukin 8 (IL-8), and beta -glucuronidase in epithelial lining fluid (ELF). We found that PE increased epithelial permeability, as measured by both the clearance of aerosolized radiolabeled albumin from the air spaces and the concentration of plasma albumin in epithelial lining fluid, but it was less effective than LPS at recruiting neutrophils into the lungs. In contrast, LPS had no significant effect on epithelium, but it increased the concentration of neutrophils, IL-8, and beta -glucuronidase in ELF. Increased epithelial permeability induced by PE does not cause lung inflammation, but it may facilitate the LPS-induced influx of neutrophils.