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Tumor Necrosis Factor Alpha Enhances Antifungal Activities of Polymorphonuclear and Mononuclear Phagocytes againstAspergillus fumigatus

机译:肿瘤坏死因子α增强了多晶核和单核吞噬细胞的抗真菌活性患者患者患者Fumigatus

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Invasive aspergillosis is a serious complication in immunocompromised patients. The effects of recombinant human tumor necrosis factor alpha (TNF-α) on antifungal activities of human neutrophils (polymorphonuclear leukocytes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macrophages (PAMs) againstAspergillus fumigatus were studied. The percentage of PMN-induced hyphal damage was increased after 30 min of incubation of PMNs with 0.1 ng of TNF-α per ml at 37°C (P = 0.043). At 0.1 to 10 ng/ml, TNF-α also increased superoxide anion (O2 ?) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN phagocytosis of conidia in the presence of serum. By comparison, TNF-α induced only a slight increase in O2 ? production by MNCs in response to phorbol myristate acetate (P = 0.05) and no concomitant increase in the percentage of MNC-induced hyphal damage. Incubation of MNCs with TNF-α at 0.001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal activity. By contrast, incubation of PAMs with TNF-α at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-α augments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity against conidia. As such, TNF-α may have an important role in host defense against aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis.
机译:侵袭性曲柄是免疫表情患者的严重并发症。重组人肿瘤坏死因子α(TNF-α)对人中性粒细胞(多核白细胞[PMNS]),人单核细胞(MNC)和兔肺肺泡巨噬细胞(PAMS)对曲霉(TNF-Collecyytes [PMNS])的影响 P = 0.043)的30分钟的PMN温育30分钟后,PMN诱导的邻苯损伤的百分比增加了30分钟的PMN。在0.1至10ng / ml时,TNF-α也增加了通过PMNS产生的超氧化物阴离子(O 2 )响应于Phorbol myristerate醋酸酯, n - 甲基硫醚苯基苯丙氨酸,单杂种菌丝( P <0.01),但对血清存在下PMN吞噬作用并未对PMN吞噬作用产生任何影响。通过比较,TNF-α仅诱导O 2 αs-sup>响应于Phorbol Myristate醋酸酯( P = 0.05)产生的略微增加跨越菌菌损伤的百分比并无伴随。用TNF-α温育在0.001至10ng / ml 2天的TNF-α对吞噬作用或分析活性没有影响。相比之下,用TNF-α孵育0.1至10ng / ml 2天的吞噬症( P = 0.03)。因此,TNF-α增加了PMN损伤曲霉菌的容量,可能通过增强的氧化机制来损害曲霉(Aspergillus 菌丝),并增加针对分枝瘤的PAM吞噬活性。因此,TNF-α可以对脑防护具有重要作用,对菱曲氏菌病,其活性的中和可能因增加对曲霉病的易感性而复杂化。

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