Salluh Jorge I, Pino Alexandre V, Silva Adriana R, Gomes Rachel N, Souza Heitor S, e Silva Jose Roberto Lapa, Jandre Frederico C, Giannella-Neto Antonio, Zimmerman Guy A, Stafforini Diana M, Prescott Stephen M, Castro-Faria-Neto Hugo C, Bozza Patrícia T, Bozza Fernando A
Immunopharmacology Laboratory, Department of Physiology and Pharmacodynamics, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Prostaglandins Leukot Essent Fatty Acids. 2007 Jul;77(1):1-8. doi: 10.1016/j.plefa.2007.04.001. Epub 2007 Jul 16.
Platelet-activating factor (PAF) is a proinflammatory mediator that plays a central role in acute lung injury (ALI). PAF- acetylhydrolases (PAF-AHs) terminate PAF's signals and regulate inflammation. In this study, we describe the kinetics of plasma and bronchoalveolar lavage (BAL) PAF-AH in the early phase of ALI. Six pigs with oleic acid induced ALI and two healthy controls were studied. Plasma and BAL samples were collected every 2h and immunohistochemical analysis of PAF-AH was performed in lung tissues. PAF-AH activity in BAL was increased at the end of the experiment (BAL PAF-AH Time 0=0.001+/-0.001 nmol/ml/min/g vs Time 6=0.031+/-0.018 nmol/ml/min/g, p=0.04) while plasma activity was not altered. We observed increased PAF-AH staining of macrophages and epithelial cells in the lungs of animals with ALI but not in healthy controls. Our data suggest that increases in PAF-AH levels are, in part, a result of alveolar production. PAF-AH may represent a modulatory strategy to counteract the excessive pro-inflammatory effects of PAF and PAF-like lipids in lung inflammation.
血小板活化因子(PAF)是一种促炎介质,在急性肺损伤(ALI)中起核心作用。PAF乙酰水解酶(PAF-AHs)可终止PAF的信号并调节炎症。在本研究中,我们描述了ALI早期血浆和支气管肺泡灌洗(BAL)中PAF-AH的动力学变化。研究了6只油酸诱导ALI的猪和2只健康对照猪。每2小时采集血浆和BAL样本,并对肺组织进行PAF-AH的免疫组织化学分析。实验结束时BAL中的PAF-AH活性增加(BAL PAF-AH时间0 = 0.001±0.001 nmol/ml/min/g,时间6 = 0.??31±0.018 nmol/ml/min/g,p = 0.04),而血浆活性未改变。我们观察到ALI动物肺中巨噬细胞和上皮细胞的PAF-AH染色增加,而健康对照中未增加。我们的数据表明,PAF-AH水平的升高部分是肺泡产生的结果。PAF-AH可能代表一种调节策略,以抵消PAF和类PAF脂质在肺部炎症中过度的促炎作用。 (注:原文中Time 6处PAF-AH数据可能有误,翻译时保留原文形式)