Zeb T, Piedboeuf B, Gamache M, Langston C, Welty S E
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Free Radic Biol Med. 1996;21(4):567-74. doi: 10.1016/0891-5849(96)00121-9.
While treatment with supplemental oxygen is often essential in patients with lung disease, prolonged therapy may cause lung injury by itself. Although the mechanisms responsible for initiating hyperoxic lung damage almost certainly involve primary oxidative transformations, the possible contributions of inflammation to the tissue injury have been attracting increasing research activity. Increases in intercellular adhesion molecule-1 (ICAM-1) coincide with the inflammation, but in other models of inflammation transient adhesion mediated by members of the Selectin gene family was found to be essential before ICAM-1/beta 2 interactions could occur. We, therefore, wondered whether a similar sequence of initial transient adhesion followed by subsequent responses would be observed in hyperoxic lung inflammation. We, therefore, determined the effects of hyperoxia exposure on lung mRNA for P- and E-Selectin in mouse lungs. We found that there was no detectable mRNA for E-Selectin through 72 h of hyperoxia exposure by Northern blotting, but that mRNA for P-Selectin was detectable as early as 48 h after initiation of hyperoxia. To determine the location of P-Selectin upregulation we examined hyperoxia-exposed mouse lungs by in situ hybridization and found that the upregulation of P-Selectin at 48 h was localized to large muscularized vessels, at 72 h expression was detected in some medium size muscularized vessels, and at 96 h abundant expression was observed also on nonmuscularized small vessels. In conclusion, increases in mRNA for P-Selectin early in the course of hyperoxia exposure suggest that P-Selectin expression in hyperoxic lungs increases in parallel with upregulation of ICAM-1, leading to the accumulation of neutrophils in hyperoxic lungs, and that interventions targeting these two adhesion molecules may lead to a diminution in hyperoxic lung inflammation and lung injury.
虽然对肺部疾病患者进行补充氧气治疗往往至关重要，但长期治疗本身可能会导致肺损伤。尽管引发高氧性肺损伤的机制几乎肯定涉及原发性氧化转化，但炎症对组织损伤的可能作用一直吸引着越来越多的研究活动。细胞间黏附分子-1（ICAM-1）的增加与炎症同时出现，但在其他炎症模型中，发现选择素基因家族成员介导的短暂黏附在ICAM-1/β2相互作用发生之前是必不可少的。因此，我们想知道在高氧性肺炎症中是否会观察到类似的初始短暂黏附随后是后续反应的序列。因此，我们确定了高氧暴露对小鼠肺中P-选择素和E-选择素mRNA的影响。我们发现，通过Northern印迹法在高氧暴露72小时内未检测到E-选择素的mRNA，但P-选择素的mRNA早在高氧开始后48小时就可检测到。为了确定P-选择素上调的位置，我们通过原位杂交检查高氧暴露的小鼠肺，发现48小时时P-选择素的上调定位于大的肌化血管，72小时时在一些中等大小的肌化血管中检测到表达，96小时时在非肌化小血管上也观察到大量表达。总之，高氧暴露早期P-选择素mRNA的增加表明，高氧肺中P-选择素的表达与ICAM-1的上调平行增加，导致中性粒细胞在高氧肺中积聚，并且针对这两种黏附分子的干预可能会减轻高氧性肺炎症和肺损伤。
