Jobin C, Kreis C, Gauthier J, Letarte J, Beaulieu A D
Unité de Recherche en Génétique Moléculaire, Hôpital St-François d'Assise, Québec City, Canada.
J Immunol. 1991 Apr 15;146(8):2701-7.
In order to investigate 5-lipoxygenase enzyme regulation in neutrophils during an inflammatory reaction, we studied 5-lipoxygenase mRNA levels, as well as de novo enzyme synthesis, in resting and activated neutrophils isolated from normal individuals and patients with rheumatoid arthritis. The approach used was to analyze these activities in resting peripheral blood neutrophils of normal individuals on the one hand and in peripheral blood and matched synovial fluid neutrophils isolated from patients with rheumatoid arthritis on the other hand. Our first observation was that resting peripheral blood neutrophils of either normal individuals or patients show detectable levels of 5-lipoxygenase mRNA and are able to synthesize the enzyme de novo. Our second observation was that inflammatory activated neutrophils from synovial fluid reveal lower 5-lipoxygenase mRNA levels and enzyme synthesis than do the patient-matched peripheral blood cells. This is in spite of the fact that, for other proteins, synovial fluid neutrophils are equally or more active than their peripheral blood counterparts. We conclude that peripheral blood neutrophils are capable of synthesizing the enzyme, thus ensuring the turnover of the protein. Furthermore, complex regulatory mechanisms appear to take place in response to inflammation as it occurs in synovial fluids of patients with rheumatoid arthritis, leading to decreased mRNA levels and enzyme synthesis. Possible mechanisms of regulation are discussed and are presently under investigation.
为了研究炎症反应期间中性粒细胞中5-脂氧合酶的酶调节，我们研究了从正常个体和类风湿性关节炎患者分离出的静息和活化中性粒细胞中的5-脂氧合酶mRNA水平以及从头酶合成。所采用的方法是一方面分析正常个体静息外周血中性粒细胞中的这些活性，另一方面分析从类风湿性关节炎患者分离出的外周血和匹配的滑液中性粒细胞中的这些活性。我们的第一个观察结果是，正常个体或患者的静息外周血中性粒细胞均显示出可检测到的5-脂氧合酶mRNA水平，并且能够从头合成该酶。我们的第二个观察结果是，滑液中炎症激活的中性粒细胞比患者匹配的外周血细胞显示出更低的5-脂氧合酶mRNA水平和酶合成。尽管对于其他蛋白质而言，滑液中性粒细胞比其外周血对应细胞同样活跃或更活跃。我们得出结论，外周血中性粒细胞能够合成该酶，从而确保蛋白质的周转。此外，似乎在类风湿性关节炎患者滑液中发生的炎症反应中会出现复杂的调节机制，导致mRNA水平和酶合成降低。讨论了可能的调节机制，目前正在研究中。
