Platelet-activating factor contributes to acute lung leak in rats given interleukin-1 intratracheally
Platelet-activating factor contributes to acute lung leak in rats given interleukin-1 intratracheally
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DOI：
10.1152/ajplung.2000.279.1.l75
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发表时间：
2000-07-01
影响因子：
4.9
通讯作者：
Repine, JE
中科院分区：
文献类型：
--
作者：
Lee, YM;Hybertson, BM;Repine, JE
急性肺损伤（ALI）患者的肺灌洗液中白细胞介素-1（IL-1）和中性粒细胞水平升高，但其与肺渗漏的关系尚不清楚。为了解决这个问题，我们研究了中性粒细胞激动剂血小板激活因子[1-O-烷基-2-乙酰基-SN-甘油-3-磷酸胆碱（PAF）]在通过气管内给予IL-1诱导的急性中性粒细胞依赖性肺漏发生中的作用。给大鼠。我们发现，PAF乙酰转移酶和PAF活性增加，在大鼠肺内注射IL-1与肺内注射生理盐水的假治疗组相比。当用WEB-2086（一种常用的PAF受体拮抗剂）治疗时，表明PAF参与了IL-1给药后肺渗漏和肺中性粒细胞蓄积的发展，肺内给予IL-1的大鼠肺渗漏减少，肺髓过氧化物酶活性降低，肺灌洗液中性粒细胞增加。此外，从经气管内给予IL-1的大鼠的肺灌洗液中回收的中性粒细胞在体外比从对照大鼠或先给予WEB-2086然后给予IL-1的大鼠中回收的中性粒细胞减少更多的硝基蓝四唑（NBT）。组织学检查表明，与对照大鼠或经WEB-2086处理后再经气管内给予IL-1的大鼠的肺相比，给予IL-1的大鼠的氯化铈染色肺切片的内皮细胞-中性粒细胞界面含有增加的过氧化铈（氯化铈与过氧化氢的反应产物）。这些体内发现得到了平行发现的支持，平行发现显示WEB-2086处理降低了体外中性粒细胞与IL-1处理的培养内皮细胞的粘附。我们的结论是，PAF有助于中性粒细胞的招聘和中性粒细胞的激活，在大鼠肺内给予IL-1。
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.