Dynamics of TGF-beta 3 peptide activity during rat alveolar epithelial cell proliferative recovery from acute hyperoxia
Dynamics of TGF-beta 3 peptide activity during rat alveolar epithelial cell proliferative recovery from acute hyperoxia
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DOI：
10.1152/ajplung.1996.271.1.l54
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发表时间：
1996-07-01
影响因子：
4.9
通讯作者：
Warburton, D
中科院分区：
文献类型：
--
作者：
Buckley, S;Bui, KC;Warburton, D
高氧导致肺损伤和恢复的可再现模式，其特征在于恢复期II型肺泡上皮细胞（AEC 2）的增殖。我们测量了成年雄性大鼠暴露于100%氧气48 h，然后在室内空气中恢复至72 h的肺中AEC 2和巨噬细胞的TGF-β肽产生，使用派-1启动子-荧光素酶水貂肺上皮细胞测定法测量TGF-β肽活性水平，并用肽特异性抑制抗体表征。对照AEC 2产生997 +/- 54 Dg活性TGF-β。10（6）个细胞（-1）。24 h（-1）（平均值+/- SD），其中> 70%为TGF-β 3，而培养的巨噬细胞产生58 +/- 17 pg活性TGF-β。10（6）个巨噬细胞（-1）。24 h（-1），> 80%为TGF-β 1。在高氧和恢复期间，AEC 2产生的活性TGF-β 3减少了75%，在恢复24 h时达到最低点（P < 0.005）。相比之下，TGF-β肽活性从对照大鼠肺灌洗液中检测不到的水平增加到45小时氧气暴露和24小时恢复后的峰值1，470 +/- 743 pg/大鼠，而培养物中灌洗液巨噬细胞TGF-β的产生也增加了三倍，达到峰值150 +/- 5 pg。10（6）个细胞（-1）。氧暴露48 h后24 h（-1），与对照组比较，差异有显著性（P < 0.005）。通过新鲜分离的AEC 2的BrdU掺入和FAGS分析确定，AEC 2活性TGF-β 3产生的最低点与AEC 2修复增殖期的峰值一致。我们的结论是，在大鼠急性高氧损伤恢复的增殖期，AEC 2的活性TGF-β 3的产生动态下调。我们推测，在急性高氧损伤的恢复过程中，TGF-β 3对AEC 2增殖的自分泌负调节作用的降低可能有助于AEC 2的增殖。
Hyperoxia causes a reproducible pattern of lung injury and recovery, characterized by proliferation of type II alveolar epithelial cells (AEC2) during the recovery phase. We measured TGF-beta peptide production by AEC2 and macrophages from lungs of adult male rats exposed to 100% oxygen for 48 h and then allowed to recover ibr up to 72 h in room air, TGF-beta peptide activity levels were measured using the PAI-1 promoter-luciferase mink lung epithelial cell assay and characterized with peptide specific inhibitory antibodies. Control AEC2 produced 997 +/- 54 Dg active TGF-beta . 10(6) cells(-1). 24 h(-1) (mean +/- SD), of which > 70% was TGF-beta 3, while cultured macrophages produced 58 +/- 17 pg active TGF-beta . 10(6) macrophages(-1). 24 h(-1), > 80% of which was TGF-beta 1. During hyperoxia and recovery; active TGF-beta 3 production by AEC2 decreased by 75%, with a nadir at 24 h recovery (P < 0.005). In contrast, TGF-beta peptide activity increased from undetectable levels in lung lavage from control rats to a peak of 1,470 +/- 743 pg/rat after 45 h oxygen exposure and 24 h recovery, while lavaged macrophage TGF-beta production in culture also increased threefold to a peak of 150 +/- 5 pg . 10(6) cells(-1). 24 h(-1) after 48 h oxygen exposure (P < 0.005). The nadir of active TGF-beta 3 production by AEC2 coincided with the peak of the AEC2 proliferative phase of repair as determined by BrdU incorporation and FAGS analysis of freshly isolated AEC2. We conclude that active TGF-beta 3 production by AEC2 is dynamically downregulated during the proliferative phase of recovery from acute hyperoxic injury in rat. We speculate that decreased autocrine negative regulation of AEC2 proliferation by TGF-beta 3 may facilitate AEC2 proliferation during recovery from acute hyperoxic injury.