A role for IL-18 in neutrophil activation
A role for IL-18 in neutrophil activation
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DOI：
10.4049/jimmunol.167.5.2879
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发表时间：
2001-09-01
影响因子：
4.4
通讯作者：
McInnes, IB
中科院分区：
文献类型：
--
作者：
Leung, BP;Culshaw, S;McInnes, IB
IL-18在几种自身免疫性和感染性疾病中的表达和功能活性已被证实。为了阐明IL-18在早期先天免疫反应中的潜在作用，我们探索了IL-18激活中性粒细胞的能力。人外周血中性粒细胞结构性地表达IL-18R(α和β)，与对IL-18快速反应的能力相称。IL-18可诱导中性粒细胞释放依赖于蛋白质合成的细胞因子和趋化因子，上调CD11b表达，促进颗粒释放，增强fMLP诱导的呼吸爆发，但对中性粒细胞凋亡率无明显影响。类风湿关节炎滑液来源的中性粒细胞释放细胞因子和趋化因子的能力显著增强，这表明对IL-18的不同反应依赖于体内先前的中性粒细胞激活。最后，IL-18促进了中性粒细胞在体内的聚集，而IL-18中和抑制了角叉菜胶注射后足垫炎症的严重程度。后者伴随着组织髓过氧化物酶表达的减少和局部肿瘤坏死因子-α的产生。总而言之，这些数据定义了IL-18在激活中性粒细胞从而促进早期先天免疫反应方面的新作用。
IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during early innate immune responses, we have explored the capacity of IL-18 to activate neutrophils. Human peripheral blood-derived neutrophils constitutively expressed IL-18R (alpha and beta) commensurate with the capacity to rapidly respond to IL-18. IL-18 induced cytokine and chemokine release from neutrophils that was protein synthesis dependent, upregulated CD11b expression, induced granule release, and enhanced the respiratory burst following exposure to fMLP, but had no effect upon the rate of neutrophil apoptosis. The capacity to release cytokine and chemokine was significantly enhanced in neutrophils derived from rheumatoid arthritis synovial fluid, indicating differential responsiveness to IL-18 dependent upon prior neutrophil activation in vivo. Finally, IL-18 administration promoted neutrophil accumulation in vivo, whereas IL-18 neutralization suppressed the severity of footpad inflammation following carrageenan injection. The latter was accompanied by reduction in tissue myeloperoxidase expression and suppressed local TNF-alpha production. Together, these data define a novel role for IL-18 in activating neutrophils and thereby promoting early innate immune responses.