Production of nitric oxide by rat alveolar macrophages stimulated by Cryptococcus neoformans or Aspergillus fumigatus
Production of nitric oxide by rat alveolar macrophages stimulated by Cryptococcus neoformans or Aspergillus fumigatus
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DOI：
10.1046/j.1365-280x.1999.00209.x
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发表时间：
1999-06-01
期刊：
影响因子：
2.9
通讯作者：
Jarstrand, C
中科院分区：
文献类型：
--
作者：
Gross, NT;Nessa, K;Jarstrand, C
新生隐球菌和烟曲霉是空气传播的真菌，肺泡巨噬细胞(AM)是宿主抵御这两种病原体的第一道防线。我们研究了体外培养的大鼠AM在新生假单胞菌、烟曲霉菌分生孢子或惰性二氧化硅颗粒单独或与干扰素-γ联合作用时产生一氧化氮(NO)的能力。研究了NO在杀灭新生葡萄球菌中的作用，以及吞噬酵母菌或烟曲霉分生孢子与AM产生NO的关系。两种真菌都能诱导AM产生少量但显著的NO，而不是惰性颗粒当每种真菌与干扰素-γ共同孵育时，AM产生的NO被协同增强，而不是二氧化硅颗粒。用干扰素-γ处理的AM和用新生弧菌攻击的AM显示出比未处理的AM更高的杀伤活性，这一发现与AM增加NO产生有关这两种作用都被NO合成的抑制剂所减弱。干扰素-γ激活的AM可增加NO的产生，同时增加对烟曲霉菌分生孢子和血清的附着量，但不影响未调理的新生隐球菌数。真菌对干扰素-γ依赖的累积黏附增加可能是真菌与干扰素-γ协同作用产生NO的原因之一。我们的数据表明，在正常宿主中，激活的大鼠AM可能有效地利用抗微生物一氧化氮系统来防御这些病原体。
Cryptococcus neoformans and Aspergillus fumigatus are airborne fungi and the alveolar macrophages (AM) constitute a first line of host defence against both pathogens. We investigated the ability of rat AM to produce nitric oxide (NO) when challenged in vitro with C. neoformans, A. fumigatus conidia or inert silica particles alone and together with interferon gamma (IFN-gamma). The role of NO in the killing of C. neoformans as well as the relationship between phagocytosis of the yeast or A. fumigatus conidia and NO production by AM were studied. Both fungi, but not the inert particles induced a small but significant increase in NO production by AM. A synergistically enhanced NO production by AM was observed when each fungus, but not silica particles, were incubated together with IFN-gamma. AM treated with IFN-gamma and challenged with C. neoformans showed higher killing activity than untreated AM, a finding that correlated with increased NO production by AM. Both effects were reduced by an inhibitor of NO synthesis. Increased NO production by IFN-gamma activated AM was found together with an increased accumulated attachment of A. fumigatus conidia and serum opsonized, but not unopsonized C. neoformans. The IFN-gamma dependent increase in accumulated attachment of the fungi might be responsible for the synergistic effect of the fungi and IFN-gamma on the NO production. Our data suggest that activated rat AM might efficiently use the antimicrobial nitric oxide system in the defence against these pathogens in the normal host.