Shamsuddin M, Anderson J, Smith L J
Pulmonary Division, Northwestern University Medical School, VA Lakeside Medical Center, Chicago, Illinois 60611-3053, USA.
Am J Respir Cell Mol Biol. 1995 Jun;12(6):697-704. doi: 10.1165/ajrcmb.12.6.7766433.
Leukotrienes (LT) and platelet-activating factor (PAF) are synthesized by several lung cells, including alveolar macrophages (AM), and may contribute to the airway inflammation that characterizes asthma. Phospholipases A2 (PLA2) can release arachidonic acid and lysophosphatidylcholine (lysoPC), precursors for leukotriene and PAF synthesis, respectively, from membrane phospholipids. The present study sought to determine the extent to which this common initial step contributes to leukotriene and PAF synthesis in rat AM. AM were obtained by lung lavage, cultured, and exposed to one or more of the following: PAF, zileuton (5-lipoxygenase inhibitor), Ro 25-4331 (dual PLA2 inhibitor), and either A23187 (Cal) or zymosan. The following measurements were made: LTB4 synthesis, PAF synthesis, and PLA2 activity. CaI stimulation increased PAF synthesis 3-fold (P < 0.001), LTB4 synthesis 20-fold (P < 0.001), and PLA2 activity 52% (P < 0.001). Incubation with PAF (2.5 microM) for 10 min decreased basal LTB4 synthesis 33% (P < 0.001), but it had no effect on basal PAF synthesis or PLA2 activity. The same dose of PAF (2.5 microM) decreased CaI-stimulated PAF synthesis 40% (P < 0.02). After CaI stimulation of PAF-pretreated cells, a relationship was found between PAF-induced changes in PLA2 activity and LTB4 synthesis (r = 0.68; P < 0.001) but not between changes in PLA2 activity and PAF synthesis. Zileuton (1 microM) decreased basal and CaI-stimulated LTB4 synthesis 50% (P < 0.02), and 80% (P < 0.002) respectively, but it did not alter PAF synthesis.
白三烯（LT）和血小板活化因子（PAF）由包括肺泡巨噬细胞（AM）在内的多种肺细胞合成，可能参与了哮喘特有的气道炎症。磷脂酶A2（PLA2）可分别从膜磷脂中释放花生四烯酸和溶血磷脂酰胆碱（lysoPC），它们分别是白三烯和PAF合成的前体。本研究旨在确定这一共同的起始步骤在大鼠AM中对白三烯和PAF合成的贡献程度。通过肺灌洗获取AM，进行培养，并使其暴露于以下一种或多种物质：PAF、齐留通（5-脂氧合酶抑制剂）、Ro 25-4331（双重PLA2抑制剂）以及A23187（Cal）或酵母聚糖。进行了以下测量：LTB4合成、PAF合成以及PLA2活性。Cal刺激使PAF合成增加3倍（P < 0.001），LTB4合成增加20倍（P < 0.001），PLA2活性增加52%（P < 0.001）。用PAF（2.5 microM）孵育10分钟可使基础LTB4合成减少33%（P < 0.001），但对基础PAF合成或PLA2活性无影响。相同剂量的PAF（2.5 microM）可使Cal刺激的PAF合成减少40%（P < 0.02）。在对PAF预处理的细胞进行Cal刺激后，发现PAF诱导的PLA2活性变化与LTB4合成之间存在相关性（r = 0.68；P < 0.001），但PLA2活性变化与PAF合成之间不存在相关性。齐留通（1 microM）分别使基础和Cal刺激的LTB4合成减少50%（P < 0.02）和80%（P < 0.002），但不改变PAF合成。
