Palmblad J, Samuelsson J, Brohult J
Department of Medicine III, Karolinska Institute, Stockholm, Sweden.
Scand J Clin Lab Invest. 1990 Jun;50(4):363-70. doi: 10.3109/00365519009091592.
We evaluated whether various alkylglycerols would initiate a functional response of human neutrophils or modify responses induced by a formyl peptide (fMLP) in vitro. We found that platelet activating factor (PAF) was the most potent with regard to the ability to produce an oxidative response (assessed by cytochrome c reduction and/or chemiluminescence), followed by ET-16-OCH3. Lyso-PAF, ET-18-OCH3, batyl- and chimyl alcohols exhibited only a weak activity. PAF was also the most efficient lipid conferring a rise of intracellular calcium concentrations ([Ca2+]i). ET-16-OCH3, ET-18-OCH3 and lysoPAF were less potent, although maximal [Ca2+]i levels were similar to that of 0.1 mumol/l fMLP. The kinetics of the calcium responses were highly specific for each ether lipid. When neutrophils had been treated with PAF or ET-18-OCH3 and were subsequently stimulated by fMLP, enhancement of the oxidative response was noted. Thus, this study shows that there was an association between the ability of an alkylglycerol to initiate oxidative and calcium responses, indicating strict structure-activity relationships for these lipids.
我们评估了多种烷基甘油是否会引发人中性粒细胞的功能反应,或在体外改变由甲酰肽(fMLP)诱导的反应。我们发现,就产生氧化反应的能力(通过细胞色素c还原和/或化学发光评估)而言,血小板活化因子(PAF)最为有效,其次是ET-16-OCH3。溶血PAF、ET-18-OCH3、鲨肝醇和神经醇仅表现出微弱的活性。PAF也是使细胞内钙浓度([Ca2+]i)升高的最有效脂质。ET-16-OCH3、ET-18-OCH3和溶血PAF的效力较低,尽管最大[Ca2+]i水平与0.1 μmol/l fMLP的相似。钙反应的动力学对每种醚脂具有高度特异性。当中性粒细胞用PAF或ET-18-OCH3处理并随后受到fMLP刺激时,氧化反应增强。因此,本研究表明烷基甘油引发氧化和钙反应的能力之间存在关联,表明这些脂质存在严格的构效关系。