Bender A, Sprenger H, Gong J H, Henke A, Bolte G, Spengler H P, Nain M, Gemsa D
Institute of Immunology, Philipps University, Marburg, Germany.
Immunobiology. 1993 Apr;187(3-5):357-71. doi: 10.1016/s0171-2985(11)80350-5.
Infection of murine PU5-1.8 macrophages and human monocytes by influenza A virus was associated with virus replication, release of tumor necrosis factor-alpha (TNF-alpha) and subsequent cell death. In the presence of small and by itself rather inefficient concentrations of lipopolysaccharide (LPS) or free lipid A (1 to 10 ng/ml), TNF-alpha production of virus-infected macrophages was strongly potentiated. LPS-triggered and enhanced TNF-alpha release from virus-infected macrophages was neither due to increased cell survival nor altered virus replication, potentiated TNF-alpha gene transcription, release of intracellularly stored TNF-alpha or shifts in the kinetics of TNF-alpha secretion. Influenza A virus infection alone induced a massive TNF-alpha mRNA accumulation which, however, was only weakly translated into bioactive TNF-alpha protein. When these virus-primed macrophages were exposed to LPS either simultaneously or up to 4 h after infection, an efficient and high translation into TNF-alpha protein occurred. Although the LPS-induced biochemical pathways leading to an augmented TNF-alpha production by virus-infected macrophages still remains unsolved, the findings suggest that the frequently observed serious clinical complications in the course of combined influenza A virus and bacterial infections may be due, at least in part, to an excessive release of cytokines such as TNF-alpha.
甲型流感病毒感染小鼠PU5-1.8巨噬细胞和人单核细胞与病毒复制、肿瘤坏死因子-α（TNF-α）的释放及随后的细胞死亡有关。在存在少量且本身效率较低的脂多糖（LPS）或游离脂质A（1至10 ng/ml）的情况下，病毒感染的巨噬细胞产生的TNF-α会被强烈增强。LPS触发并增强病毒感染巨噬细胞释放TNF-α，这既不是由于细胞存活率增加，也不是由于病毒复制改变、TNF-α基因转录增强、细胞内储存的TNF-α释放或TNF-α分泌动力学的改变。单独的甲型流感病毒感染会诱导大量TNF-α mRNA积累，然而，这些mRNA仅微弱地翻译成具有生物活性的TNF-α蛋白。当这些经病毒预处理的巨噬细胞在感染后同时或长达4小时暴露于LPS时，会高效且大量地翻译成TNF-α蛋白。尽管LPS诱导的导致病毒感染巨噬细胞TNF-α产生增加的生化途径仍未解决，但这些发现表明，在甲型流感病毒和细菌合并感染过程中经常观察到的严重临床并发症可能至少部分归因于细胞因子如TNF-α的过度释放。
