Lee Y M, Hybertson B M, Cho H G, Terada L S, Cho O, Repine A J, Repine J E
Webb Waring Institute for Cancer, Aging, and Antioxidant Research at the University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Am J Physiol Lung Cell Mol Physiol. 2000 Jul;279(1):L75-80. doi: 10.1152/ajplung.2000.279.1.L75.
Lung lavage fluid of patients with acute lung injury (ALI) has increased levels of interleukin-1 (IL-1) and neutrophils, but their relationship to the lung leak that characterizes these patients is unclear. To address this concern, we investigated the role of the neutrophil agonist platelet-activating factor [1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF)] in the development of the acute neutrophil-dependent lung leak that is induced by giving IL-1 intratracheally to rats. We found that PAF acetyltransferase and PAF activities increased in lungs of rats given IL-1 intratracheally compared with lungs of sham-treated rats given saline intratracheally. The participation of PAF in the development of lung leak and lung neutrophil accumulation after IL-1 administration was suggested when treatment with WEB-2086, a commonly used PAF-receptor antagonist, decreased lung leak, lung myeloperoxidase activity, and lung lavage fluid neutrophil increases in rats given IL-1 intratracheally. Additionally, neutrophils recovered from the lung lavage fluid of rats given IL-1 intratracheally reduced more nitro blue tetrazolium (NBT) in vitro than neutrophils recovered from control rats or rats that had been given WEB-2086 and then IL-1. Histological examination indicated that the endothelial cell-neutrophil interfaces of cerium chloride-stained lung sections of rats given IL-1 contained increased cerium perhydroxide (the reaction product of cerium chloride with hydrogen peroxide) compared with lungs of control rats or rats treated with WEB-2086 and then given IL-1 intratracheally. These in vivo findings were supported by parallel findings showing that WEB-2086 treatment decreased neutrophil adhesion to IL-1-treated cultured endothelial cells in vitro. We concluded that PAF contributes to neutrophil recruitment and neutrophil activation in lungs of rats given IL-1 intratracheally.
急性肺损伤（ALI）患者的肺灌洗液中白细胞介素-1（IL-1）水平和中性粒细胞数量增加，但其与这些患者所特有的肺渗漏之间的关系尚不清楚。为了解决这一问题，我们研究了中性粒细胞激动剂血小板活化因子[1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱（PAF）]在经气管内给予大鼠IL-1诱导的急性中性粒细胞依赖性肺渗漏发生过程中的作用。我们发现，与经气管内给予生理盐水的假手术处理大鼠的肺相比，经气管内给予IL-1的大鼠肺中PAF乙酰转移酶和PAF活性增加。当使用常用的PAF受体拮抗剂WEB-2086进行治疗可减少经气管内给予IL-1的大鼠的肺渗漏、肺髓过氧化物酶活性以及肺灌洗液中性粒细胞增加时，提示PAF参与了IL-1给药后肺渗漏和肺中性粒细胞聚集的发生。此外，与从对照大鼠或给予WEB-然后IL-1的大鼠回收的中性粒细胞相比，从经气管内给予IL-1的大鼠肺灌洗液中回收的中性粒细胞在体外还原更多的硝基蓝四唑（NBT）。组织学检查表明，与对照大鼠或经WEB-2086处理然后经气管内给予IL-1的大鼠的肺相比，经气管内给予IL-1的大鼠氯化铈染色肺切片的内皮细胞-中性粒细胞界面含有更多的过氢氧化铈（氯化铈与过氧化氢的反应产物）。这些体内研究结果得到了平行研究结果的支持，即WEB-2086治疗在体外可减少中性粒细胞对经IL-1处理的培养内皮细胞的粘附。我们得出结论，PAF有助于经气管内给予IL-1的大鼠肺中中性粒细胞的募集和激活。
