ETHANOL SUPPRESSES MYCOBACTERIA TUBERCULOSIS-INDUCED MESSENGER-RNA FOR NITRIC-OXIDE SYNTHASE IN ALVEOLAR MACROPHAGES, IN-VIVO
ETHANOL SUPPRESSES MYCOBACTERIA TUBERCULOSIS-INDUCED MESSENGER-RNA FOR NITRIC-OXIDE SYNTHASE IN ALVEOLAR MACROPHAGES, IN-VIVO
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DOI：
10.1111/j.1530-0277.1995.tb01521.x
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发表时间：
1995-04-01
影响因子：
3.2
通讯作者：
MASON, C
中科院分区：
文献类型：
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作者：
GREENBERG, S;XIE, JM;MASON, C
急性摄入酒精[乙醇（ETOH）]会对初次接触者和慢性酒精滥用者的免疫能力产生不利影响。在长期酗酒者中发现结核病的发病率和严重程度增加。肺泡巨噬细胞（AM）产生的一氧化氮（NO）在体外对鸟分枝杆菌（Mycobacterium avium）和结核分枝杆菌（Mycobacterium tuberculosis，MTB）的杀伤中起重要作用。我们实验室最近的研究表明，ETOH抑制内毒素诱导的AM中TNF-α和NO的增加。我们测试的假设，急性摄入ETOH可以干扰分枝杆菌诱导的AM中NO系统的上调，在体内。我们表明，热杀死M。禽流感病毒复合物（MAC）和人MTB毒力灌入大鼠肺后，支气管肺泡灌洗液（BAL液）中AM诱导型NO合酶II（iNOS）mRNA表达迅速增加。这与BAL液、肺匀浆和AM中活性氮中间体[（RNI）; NO2-和NO3-]的产生相关，而BAL液TNF-α无显著增加。在气管内给予MAC或MTB前30分钟给予单剂量ETCH（5.5 g/kg，ip）可减弱MAC和MTB诱导的BAL液、肺和AM中RNI的增加以及iNOS mRNA的增加。因此，分枝杆菌上调iNOSmRNA并增强AM的RNI产生，而不增加TNF-α的产生。此外，在ETOH介导的TNF抑制不存在的情况下，ETOH减弱分枝杆菌诱导的iNOS和RNI产生的mRNA上调。推测ETCH介导的AM NO系统的抑制可能为分枝杆菌感染的严重性增加提供了一种解释。酗酒者的感染
Acute ingestion of alcohol [ethanol (ETOH)] adversely affects the immunocompetence of both naive individuals as well as chronic alcohol abusers. An increased incidence and severity of tuberculosis is found in chronic alcohol abusers. Nitric oxide (NO) produced by alveolar macrophages (AMs) may play a role in the in vitro killing of Mycobacterium avium and Mycobacterium tuberculosis (MTB), Moreover, tumor necrosis factor-alpha (TNF-alpha) is believed to be a primary cytokine mediator of NO production by AMs. Recent studies from our laboratory demonstrated that ETOH suppressed endotoxin-induced increases in both TNF-alpha and NO in AMs, in vivo. We tested the postulate that acute ingestion of ETOH can interfere with mycobacteria-induced upregulation of the NO system in AMs, in vivo. We show that heat-killed M. avium complex (MAC) and human virulent MTB instilled into rat lungs rapidly increased mRNA for inducible NO synthase II (iNOS) of AMs in fluid obtained by bronchoalveolar lavage (BAL fluid). This was associated with production of reactive nitrogen intermediates [(RNIs); NO2,- and NO3-] in BAL fluid, lung homogenate, and AMs in the absence of a significant increase in BAL fluid TNF-alpha. A single dose of ETCH (5.5 g/kg, ip) administered 30 min before intratracheal administration of MAC or MTB attenuated both MAC and MTB-induced increases in RNI in BAL fluid, lung, and AMs, and the increase in mRNA for iNOS. Thus, mycobacteria upregulate iNOS mRNA and enhance RNI production by AMs without any increase in the production of TNF-alpha. Moreover, ETOH attenuates mycobacteria-induced upregulation of mRNA for iNOS and RNI production in the absence of ETOH-mediated suppression of TNF. Speculatively, ETCH-mediated inhibition of the AM NO system may offer an explanation for the increased severity of mycobacterial in. fections in alcoholics.