Killing of Klebsiella pneumoniae by human alveolar macrophages
Killing of Klebsiella pneumoniae by human alveolar macrophages
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DOI：
10.1152/ajplung.00216.2001
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发表时间：
2002-05-01
影响因子：
4.9
通讯作者：
Matalon, S
中科院分区：
文献类型：
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作者：
Hickman-Davis, JM;O'Reilly, P;Matalon, S
我们研究了人肺表面活性蛋白A(SP-A)通过从肺移植患者的支气管肺泡灌洗液中分离出来的人肺泡巨噬细胞(AM)对肺炎克雷伯菌的杀灭作用的可能机制。与未加SP-A的克雷伯氏菌感染的AM相比，与人SP-A(25µg/ml)和克雷伯氏菌共孵育120min，AM的总集落形成单位减少68%，这种作用可被N-G-单甲基-L-精氨酸所阻断。移植肺泡巨噬细胞与SP-A孵育后，细胞内钙离子浓度([Ca~(2+)](I))增加70%，亚硝酸盐和硝酸盐(NOx)产生增加45%(从0.24+/-0.02增加到1.3+/-0.21nmol.10(6)AM(-1))。H(-1))。用1，2-双(2-氨基苯氧基)乙烷-N，N，N‘，N’-四乙酸乙酰氧甲酯预育可抑制细胞内[Ca~(2+)]~(2+)浓度升高，抑制SP-A介导的克雷伯氏菌吞噬和杀伤作用。相反，来自正常志愿者的AM与SP-A孵育后，[Ca~(2+)](I)和NOx的产生都减少了，并且没有导致克雷伯菌的杀灭。在无细胞体系中，在pH值为5时持续产生过氧亚硝酸盐(>；1微米/分钟)也可显著杀灭克雷伯氏菌，但在pH值为7.4时则不能。这些发现表明，SP-A通过刺激吞噬和产生活性氧-氮中间产物来介导移植肺AM对病原体的杀灭。
We investigated putative mechanisms by which human surfactant protein A (SP-A) effects killing of Klebsiella pneumoniae by human alveolar macrophages (AMs) isolated from bronchoalveolar lavagates of patients with transplanted lungs. Coincubation of AMs with human SP-A (25 mug/ml) and Klebsiella resulted in a 68% decrease in total colony forming units by 120 min compared with AMs infected with Klebsiella in the absence of SP-A, and this SP-A-mediated effect was abolished by preincubation with N-G-monomethyl-L-arginine. Incubation of transplant AMs with SP-A increased intracellular Ca2+ concentration ([Ca2+](i)) by 70% and nitrite and nitrate (NOx) production by 45% (from 0.24 +/- 0.02 to 1.3 +/- 0.21 nmol.10(6) AMs(-1) . h(-1)). Preincubation with 1,2- bis( 2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester inhibited the increase in [Ca2+](i) and abrogated the SP-A-mediated Klebsiella phagocytosis and killing. In contrast, incubation of AMs from normal volunteers with SP-A decreased both [Ca2+](i) and NOx production and did not result in killing of Klebsiella. Significant killing of Klebsiella was also seen in a cell-free system by sustained production of peroxynitrite (>1 muM/min) at pH 5 but not at pH 7.4. These findings indicate that SP-A mediates pathogen killing by AMs from transplant lungs by stimulating phagocytosis and production of reactive oxygen-nitrogen intermediates.