Weller P F, Lee C W, Foster D W, Corey E J, Austen K F, Lewis R A
Proc Natl Acad Sci U S A. 1983 Dec;80(24):7626-30. doi: 10.1073/pnas.80.24.7626.
5-Lipoxygenase pathway-derived products of arachidonic acid released by human eosinophils activated in vitro have been measured by using radioimmunoassays specific for leukotriene B4 (LTB4) and for sulfidopeptide leukotrienes including leukotriene C4 (LTC4). Eosinophil-enriched leukocytes (mean, 85% eosinophils) from five hypereosinophilic donors activated with 5.0 microM ionophore A23187 for 15 min at 37 degrees C in the presence of 50 mM L-serine released 69 +/- 28 and 1.5 +/- 0.8 (mean +/- SEM) ng of LTC4 and LTB4, respectively, per 10(6) cells; ratios of LTC4 to LTB4 ranged from 16 to 149. Eosinophils stimulated with ionophore (2.5 microM) or phorbol myristate acetate (1 microgram per ml) metabolized exogenously added LTC4 to products that coeluted on reverse-phase high-performance liquid chromatography with synthetic S-diastereoisomeric LTC4 sulfoxides and 6-trans-LTB4 diastereoisomers, and this metabolic inactivation was inhibited by L-serine or catalase. Ionophore-activated eosinophils purified from three normal donors also preferentially generated LTC4 (38 +/- 3 ng per 10(6) cells) relative to LTB4 (6.0 +/- 3.1 ng per 10(6) cells), whereas neutrophils from the same donors released LTB4 (48 +/- 21 ng per 10(6) cells) in a greater than 7-fold excess to LTC4. The predominant production by human eosinophils of LTC4 with its potent smooth muscle spasmogenic and vasoactive properties may contribute to the pathobiology of allergic and other diseases associated with eosinophilia.
通过使用对白三烯B4（LTB4）和包括白三烯C4（LTC4）在内的硫肽白三烯具有特异性的放射免疫分析法，对体外激活的人嗜酸性粒细胞释放的花生四烯酸的5-脂氧合酶途径衍生产物进行了测定。来自5名嗜酸性粒细胞增多症供体的富含嗜酸性粒细胞的白细胞（平均85%为嗜酸性粒细胞），在50 mM L-丝氨酸存在下，于37℃用5.0 microM离子载体A23187激活15分钟，每10⁶个细胞分别释放69±28和1.5±0.8（平均±标准误）ng的LTC4和LTB4；LTC4与LTB4的比率在16至149之间。用离子载体（2.5 microM）或佛波酯肉豆蔻酸酯乙酸盐（每毫升1微克）刺激的嗜酸性粒细胞将外源性添加的LTC4代谢为在反相高效液相色谱上与合成的S-非对映异构体LTC4亚砜和6-反式-LTB4非对映异构体共洗脱的产物，这种代谢失活受到L-丝氨酸或过氧化氢酶的抑制。从3名正常供体纯化的经离子载体激活的嗜酸性粒细胞相对于LTB4（每10⁶个细胞6.0±3.1 ng）也优先产生LTC4（每10⁶个细胞38±3 ng），而来自相同供体的中性粒细胞释放的LTB4（每10⁶个细胞48±21 ng）比LTC4多出7倍以上。人嗜酸性粒细胞主要产生具有强大平滑肌痉挛和血管活性特性的LTC4，这可能有助于与嗜酸性粒细胞增多相关的过敏性和其他疾病的病理生物学过程。
