Djeu J Y, Matsushima K, Oppenheim J J, Shiotsuki K, Blanchard D K
University of South Florida College of Medicine, Department of Medical Microbiology and Immunology, Tampa 33612.
J Immunol. 1990 Mar 15;144(6):2205-10.
Monocyte-derived neutrophil chemotactic factor (MDNCF)/IL-8, a novel cytokine, distinct from IL-1 and TNF was recently purified and cloned. This study was performed to investigate the biologic effect of recombinant MDNCF/IL-8 on human polymorphonuclear neutrophils (PMN) by assessment of their growth inhibitory activity against Candida albicans. The chemoattractant, FMLP was used as a positive control. We demonstrated that MDNCF/IL-8, similar to FMLP, effectively enhanced PMN-mediated anti-Candida activity. MDNCF/IL-8, from 1.0 to 1000 ng/mol, enhanced PMN-mediated anti-Candida activity, whereas FMLP was effective from 10(-10) to 10(-7) M. The optimal dose of MDNCF/IL-8 for PMN stimulation was 10 ng/ml which equalled the optimal chemoattractant dose. MDNCF/IL-8 itself, like FMLP, had no direct effect on Candida growth at any concentration and it stimulated antifungal activity only in PMN but not in monocytes. Interestingly, MDNCF/IL-8 failed to stimulate directly the production of superoxide from PMN or prime the respiratory burst of PMN exposed to FMLP. However, MDNCF/IL-8 was capable of releasing azurophilic enzymes from cytochalasin B-treated PMN into the extracellular space. Enhancement of PMN anti-Candida activity and release of azurophilic enzymes from PMN by MDNCF/IL-8 were inhibited in the presence of colchicine, which is a known inhibitor of degranulation. These results suggest that MDNCF/IL-8 induced antifungal action of PMN via oxygen-independent pathways. Furthermore, MDNCF/IL-8 induction of anti-Candida action by PMN was inhibited by pretreatment with Bordetella pertussis toxin, suggesting that enhancement of PMN antifungal activity by MDNCF/IL-8, as well as by FMLP, may be mediated by a GTP-binding protein.
单核细胞衍生的中性粒细胞趋化因子（MDNCF）/白细胞介素-8，一种不同于白细胞介素-1和肿瘤坏死因子的新型细胞因子，最近已被纯化和克隆。本研究旨在通过评估重组MDNCF/白细胞介素-8对白色念珠菌的生长抑制活性，来研究其对人多形核中性粒细胞（PMN）的生物学效应。趋化剂N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（FMLP）用作阳性对照。我们证明，与FMLP相似，MDNCF/白细胞介素-8能有效增强PMN介导的抗念珠菌活性。MDNCF/白细胞介素-8在1.0至1000纳克/摩尔范围内增强PMN介导的抗念珠菌活性，而FMLP在10⁻¹⁰至10⁻⁷摩尔范围内有效。刺激PMN的MDNCF/白细胞介素-8的最佳剂量为10纳克/毫升，这与最佳趋化剂剂量相当。MDNCF/白细胞介素-8本身，与FMLP一样，在任何浓度下对念珠菌生长均无直接影响，且仅在PMN中而非单核细胞中刺激抗真菌活性。有趣的是，MDNCF/白细胞介素-8无法直接刺激PMN产生超氧化物，也不能引发暴露于FMLP的PMN的呼吸爆发。然而，MDNCF/白细胞介素-8能够将细胞松弛素B处理过的PMN中的嗜天青颗粒酶释放到细胞外空间。在存在秋水仙碱（一种已知的脱颗粒抑制剂）的情况下，MDNCF/白细胞介素-8对PMN抗念珠菌活性的增强作用以及从PMN中释放嗜天青颗粒酶的作用均受到抑制。这些结果表明，MDNCF/白细胞介素-8通过不依赖氧的途径诱导PMN的抗真菌作用。此外，百日咳博德特氏菌毒素预处理可抑制MDNCF/白细胞介素-8诱导的PMN抗念珠菌作用，这表明MDNCF/白细胞介素-8以及FMLP对PMN抗真菌活性的增强作用可能由一种GTP结合蛋白介导。
