Harvath L, Aksamit R R
J Immunol. 1984 Sep;133(3):1471-6.
F-met-leu-phe, a potent neutrophil and monocyte chemoattractant, can be oxidized to F-met-leu-phe sulfoxide by metabolically activated neutrophils. We investigated the interaction of human neutrophils and monocytes with chemically prepared oxidized derivatives of F-met-leu-phe: F-met-leu-phe sulfoxide and F-met-leu-phe sulfone. We compared the derivatives with nonoxidized parent F-met-leu-phe for specific binding to neutrophils and monocytes, and for effectiveness as chemoattractants and stimuli of superoxide production. We observed that neutrophils did not migrate to either derivative over the concentration range of 10(-9) to 10(-3) M. In marked contrast, monocytes migrated to both oxidized peptides, with optimal chemotaxis occurring at derivative concentrations 10- to 100-fold higher than the optimal parent F-met-leu-phe concentration. F-met-leu-phe sulfoxide and sulfone stimulated neutrophil and monocyte superoxide production and specifically bound to both neutrophils and monocytes at optimal concentrations that were 10- to 100-fold greater than the optimal parent F-met-leu-phe concentration. These results suggest that the higher concentrations of oxidized derivatives required for monocyte migration and for neutrophil and monocyte superoxide production are due to a reduced affinity of the oxidized derivatives for the F-met-leu-phe receptor. The finding that oxidized F-met-leu-phe binds to the neutrophil receptor without eliciting a chemotactic response suggests that the F-met-leu-phe receptor complex or chemotaxis transduction mechanism is different in human neutrophils and monocytes.
F-甲硫-亮-苯丙氨酸是一种强效的中性粒细胞和单核细胞趋化因子，可被代谢激活的中性粒细胞氧化为F-甲硫-亮-苯丙氨酸亚砜。我们研究了人类中性粒细胞和单核细胞与化学合成的F-甲硫-亮-苯丙氨酸氧化衍生物：F-甲硫-亮-苯丙氨酸亚砜和F-甲硫-亮-苯丙氨酸砜之间的相互作用。我们将这些衍生物与未氧化的母体F-甲硫-亮-苯丙氨酸进行比较，以观察它们与中性粒细胞和单核细胞的特异性结合情况，以及作为趋化因子和超氧化物产生刺激物的有效性。我们观察到，在10^(-9)至10^(-3) M的浓度范围内，中性粒细胞不会向任何一种衍生物迁移。与之形成鲜明对比的是，单核细胞会向两种氧化肽迁移，最佳趋化作用出现在衍生物浓度比母体F-甲硫-亮-苯丙氨酸的最佳浓度高10至100倍时。F-甲硫-亮-苯丙氨酸亚砜和砜刺激中性粒细胞和单核细胞产生超氧化物，并在比母体F-甲硫-亮-苯丙氨酸的最佳浓度高10至100倍的最佳浓度下与中性粒细胞和单核细胞特异性结合。这些结果表明，单核细胞迁移以及中性粒细胞和单核细胞产生超氧化物所需的氧化衍生物浓度较高，是由于氧化衍生物与F-甲硫-亮-苯丙氨酸受体的亲和力降低所致。氧化的F-甲硫-亮-苯丙氨酸与中性粒细胞受体结合但不引发趋化反应，这一发现表明人类中性粒细胞和单核细胞中的F-甲硫-亮-苯丙氨酸受体复合物或趋化转导机制有所不同。
