Thompson Lauree R, Keeney Susan E, Tarrant Donna, Rudloff Elizabeth, Dallas Dara V, Schmalstieg Frank C
Department of Pediatrics, Route 0526, University of Texas Medical Branch, Galveston, Texas 77555-0526, USA.
Inflammation. 2004 Jun;28(3):147-57. doi: 10.1023/b:ifla.0000039561.37868.91.
Sublethal doses of LPS result in increased tolerance to high concentrations of oxygen and this is associated with decreased pulmonary inflammation in a rat model. To investigate the mechanism of decreased neutrophil influx into the lung in this model, we measured levels of mRNA in the lung for the endothelial adhesion molecules, E-selectin and P-selectin. Immunostaining for E-selectin protein was also done in rat lungs, as well as measurement of soluble L-selectin in the blood. These levels were measured in the lungs of adult rats injected with 0.5 mg/kg LPS or placebo at 0 and 24 h and exposed to > 95% O2 for 60 h. Oxygen exposure resulted in significant increases in both E- and P-selectin mRNA and in E-selectin protein after 60 h. LPS resulted in an early rise in E-selectin protein followed by a decline to less than control (saline/O2) levels at 60 h. Messenger RNA for E-selectin followed a similar trend, although there were no differences at 60 h between LPS and control groups exposed to O2. P-selectin mRNA expression did not significantly differ between LPS and control O2 groups. Soluble L-selectin levels decreased by 6 h after LPS infusion and were significantly lower than saline/O2 controls through 24 h, suggesting binding to endothelium. In conclusion, the decrease in E-selectin expression on the surface of pulmonary endothelium after LPS could contribute to decreased inflammation in this model of oxygen toxicity. Soluble L-selectin may serve a further anti-inflammatory role after LPS infusion by binding to pulmonary endothelium.
亚致死剂量的脂多糖(LPS)可导致对高浓度氧气的耐受性增加,这与大鼠模型中肺部炎症的减轻有关。为了研究该模型中中性粒细胞向肺内流入减少的机制,我们测量了肺中内皮粘附分子E-选择素和P-选择素的mRNA水平。还对大鼠肺组织进行了E-选择素蛋白的免疫染色,并测量了血液中可溶性L-选择素的水平。在0小时和24小时给成年大鼠注射0.5mg/kg LPS或安慰剂,并使其暴露于>95%氧气中60小时,然后测量这些水平。氧气暴露60小时后,E-选择素和P-选择素的mRNA以及E-选择素蛋白均显著增加。LPS导致E-选择素蛋白早期升高,随后在60小时时降至低于对照组(生理盐水/氧气)水平。E-选择素的信使RNA也呈现类似趋势,尽管在暴露于氧气的LPS组和对照组之间,60小时时没有差异。LPS组和对照组氧气组之间P-选择素mRNA表达没有显著差异。LPS输注后6小时可溶性L-选择素水平下降,并且在24小时内显著低于生理盐水/氧气对照组,提示其与内皮细胞结合。总之,LPS后肺内皮表面E-选择素表达的降低可能有助于减轻该氧中毒模型中的炎症。可溶性L-选择素在LPS输注后可能通过与肺内皮结合发挥进一步的抗炎作用。