Goetzl E J, Austen K F
Department of Medicine, Harvard Medical School and Robert B. Brigham Hospital, Boston, Massachusetts 02120, USA.
J Clin Invest. 1974 Feb;53(2):591-9. doi: 10.1172/JCI107594.
The interaction of human neutrophils adherent to plastic petri dishes with the purified chemotactic factors C5a and kallikrein increased their rate of aerobic glycolysis 25-120% and the activity of their hexose monophosphate shunt (HMPS) 100-600%, reaching a plateau after 2 hr at 37 degrees C. The stimulation of either pathway required a chemotactically active stimulus since neither C5 nor prekallikrein or inactivated kallikrein could enhance metabolic activity. Marked suppression of the neutrophil chemotactic response by preincubation with a chemotactic factor to achieve deactivation, 5 x 10(-7) M diisopropyl fluorophosphate, or the neutrophil immobilizing factor (NIF) did not prevent the stimulation of HMPS activity or glycolysis by chemotactic factors. The metabolic inhibitors iodoacetate and 6-aminonicotinamide at concentrations which blocked enhancement of glycolysis or HMPS activity, respectively, partially suppressed the chemotactic response of neutrophils to the chemotactic factors. The capacity of a chemotactic factor to stimulate glucose metabolism of human neutrophils is associated with a maximal chemotactic response, but this stimulation is not alone sufficient for chemotaxis.
黏附于塑料培养皿的人中性粒细胞与纯化的趋化因子C5a和激肽释放酶相互作用,使其有氧糖酵解速率提高了25%-120%,其磷酸己糖旁路(HMPS)活性提高了100%-600%,在37℃下2小时后达到平稳状态。两条途径的刺激都需要趋化活性刺激,因为C5、前激肽释放酶或失活的激肽释放酶都不能增强代谢活性。通过与趋化因子预孵育以实现失活,用5×10⁻⁷M二异丙基氟磷酸或中性粒细胞固定因子(NIF)对中性粒细胞趋化反应进行显著抑制,并不能阻止趋化因子对HMPS活性或糖酵解的刺激。碘乙酸和6-氨基烟酰胺这两种代谢抑制剂,分别在阻断糖酵解增强或HMPS活性增强的浓度下,部分抑制了中性粒细胞对趋化因子的趋化反应。趋化因子刺激人中性粒细胞葡萄糖代谢的能力与最大趋化反应相关,但这种刺激本身不足以引起趋化作用。