Yagisawa M, Yuo A, Kitagawa S, Yazaki Y, Togawa A, Takaku F
Research Institute, International Medical Center of Japan, Tokyo.
Exp Hematol. 1995 Jul;23(7):603-8.
Together, interleukin-1 alpha (IL-1 alpha) and IL-1 beta primed human neutrophils for enhanced release of superoxide (O2-) stimulated by chemotactic peptide, chemokine, and plant lectin, and alone, each triggered O2- release in a dose-dependent manner. The maximal priming and triggering effect was obtained by high concentrations (50 to 500 ng/mL) of IL-1 alpha or IL-1 beta, though IL-1 beta was more effective than IL-1 alpha at suboptimal concentrations. Priming effect of IL-1 was very rapid and maximal within 10 minutes, whereas O2- release triggered by IL-1 was gradual and continued for 90 to 120 minutes. Combined stimulation of human neutrophils with IL-1 plus granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF) resulted in additive priming effect, and combined stimulation of neutrophils with IL-1 plus G-CSF, GM-CSF, or tumor necrosis factor (TNF) resulted in additive triggering effect, even when the maximal concentration of each cytokine was used. These priming and triggering effects of IL-1 alpha and IL-1 beta on the respiratory burst in human neutrophils were completely inhibited by IL-1 receptor antagonist (IL-1ra). Furthermore, only the net effect of IL-1 was inhibited by IL-1ra, even when human neutrophil was stimulated with IL-1 plus other cytokines to release O2-. Present results indicate that IL-1 does stimulate the respiratory burst activity in human neutrophils via receptor-mediated mechanism and suggest that the post-IL-1-receptor signaling pathways linked to the activation system of the respiratory burst are independent from those utilized by other cytokines in human neutrophils.
白细胞介素-1α（IL-1α）和白细胞介素-1β（IL-1β）共同作用时，可使人类中性粒细胞致敏，从而增强趋化肽、趋化因子和植物凝集素刺激下超氧化物（O2-）的释放；单独作用时，二者均可剂量依赖性地触发O2-释放。高浓度（50至500 ng/mL）的IL-1α或IL-1β可产生最大的致敏和触发效应，不过在次优浓度下，IL-1β比IL-1α更有效。IL-1的致敏作用非常迅速，在10分钟内达到最大值，而IL-1触发的O2-释放则较为缓慢，并持续90至120分钟。IL-1与粒细胞集落刺激因子（G-CSF）或粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合刺激人类中性粒细胞可产生相加的致敏效应，IL-1与G-CSF、GM-CSF或肿瘤坏死因子（TNF）联合刺激中性粒细胞可产生相加的触发效应，即使使用每种细胞因子的最大浓度也是如此。IL-1α和IL-1β对人类中性粒细胞呼吸爆发的这些致敏和触发效应被白细胞介素-1受体拮抗剂（IL-1ra）完全抑制。此外，即使人类中性粒细胞用IL-1加其他细胞因子刺激以释放O2-，IL-1ra也仅抑制IL-1的净效应。目前的结果表明，IL-1确实通过受体介导的机制刺激人类中性粒细胞的呼吸爆发活性，并表明与呼吸爆发激活系统相关的IL-1受体后信号通路独立于人类中性粒细胞中其他细胞因子所利用的信号通路。
