Stenke L, Samuelsson J, Palmblad J, Dabrowski L, Reizenstein P, Lindgren J A
Department of Physiological Chemistry, Karolinska Institutet, Stockholm, Sweden.
Br J Haematol. 1990 Mar;74(3):257-63. doi: 10.1111/j.1365-2141.1990.tb02580.x.
Leukotriene (LT) formation was studied in ionophore A23187-stimulated white blood cell (WBC) preparations from patients with chronic myelogenous leukaemia (CML; n = 14), polycythaemia vera (PV; n = 10) and two control groups consisting of patients with non-malignant inflammatory disease (n = 4) and normal healthy donors (n = 25). The synthesized products were identified and quantitated using high-performance liquid chromatography combined with computerized UV-spectroscopy. White blood cell preparations from the CML patients produced more LTC4 (40.2 +/- 7.9 pmol/10(6) WBC, mean +/- SEM) than WBC from the healthy donors (9.0 +/- 1.8), P less than 0.0005. In contrast, the formation of LTB4 was normal and there was no increase in the total leukotriene synthesis (the sum of LTC4, LTB4, 20-OH-LTB4 and the delta 6-trans-isomers of LTB4). The ratio between leukotrienes C4 and B4 was strongly elevated in the CML group; 1.67 +/- 0.25 v. 0.37 +/- 0.07 in the controls, P less than 0.0005. No significant correlation was observed between the levels of LTC4 and the number of known LTC4 producing cells (such as monocytes, eosinophils and basophils) in the CML WBC preparations. In contrast, a correlation was found between the sum of neutrophilic granulocytes and metamyelocytes in these suspensions and the amount of LTB4 formed; r = 0.600, P less than 0.05. A number of other laboratory or clinical variables of the CML patients (including total white blood cell and platelet counts, differential counts, previous cytotoxic treatment, time from diagnosis, time from last treatment, post study survival and age) did not significantly correlate with the formation of leukotrienes. No abnormality in the production of LTB4 or LTC4 was observed in granulocyte and WBC preparations from the patients with polycythaemia vera and non-malignant inflammatory disease, respectively. The results indicate a selectively increased LTC4 producing capacity in CML.
研究了慢性粒细胞白血病（CML；n = 14）、真性红细胞增多症（PV；n = 10）患者以及由非恶性炎症性疾病患者（n = 4）和正常健康供者（n = 25）组成的两个对照组的离子载体A23187刺激的白细胞（WBC）制剂中白三烯（LT）的形成。使用高效液相色谱结合计算机化紫外光谱法对合成产物进行鉴定和定量。CML患者的白细胞制剂产生的LTC4（40.2±7.9 pmol/10⁶WBC，平均值±标准误）比健康供者的白细胞（9.0±1.8）更多，P<0.0005。相比之下，LTB4的形成正常，白三烯的总合成量（LTC4、LTB4、20-OH-LTB4和LTB4的δ6-反式异构体之和）没有增加。CML组中白三烯C4与B4的比例显著升高；对照组为1.67±0.25，而对照组为0.37±0.07，P<0.0005。在CML的WBC制剂中，未观察到LTC4水平与已知产生LTC4的细胞（如单核细胞、嗜酸性粒细胞和嗜碱性粒细胞）数量之间存在显著相关性。相比之下，在这些悬浮液中嗜中性粒细胞和晚幼粒细胞的总数与形成的LTB4量之间存在相关性；r = 0.600，P<0.05。CML患者的许多其他实验室或临床变量（包括白细胞和血小板总数、分类计数、先前的细胞毒性治疗、诊断时间、上次治疗时间、研究后生存期和年龄）与白三烯的形成没有显著相关性。在真性红细胞增多症患者的粒细胞和WBC制剂以及非恶性炎症性疾病患者中，分别未观察到LTB4或LTC4产生异常。结果表明CML中产生LTC4的能力选择性增加。
