Matsunaga Kazuto, Klein Thomas W, Friedman Herman, Yamamoto Yoshimasa
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Florida 33612-4799, USA.
Clin Diagn Lab Immunol. 2002 Jul;9(4):864-71. doi: 10.1128/cdli.9.4.864-871.2002.
Even though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication of Legionella pneumophila in macrophages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-alpha production by macrophages in response to infection. The results of exogenous TNF-alpha treatment and neutralization treatment with anti-TNF-alpha and anti-gamma-interferon (IFN-gamma) antibodies and the determination of IFN-gamma mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibit L. pneumophila growth by up-regulation of TNF-alpha and IFN-gamma production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages to L. pneumophila infection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.
尽管吸烟已被证明会抑制肺部的免疫反应，但关于香烟烟雾成分对呼吸道感染的影响却知之甚少。在本研究中，检测了香烟烟雾冷凝物（CSC）对肺泡巨噬细胞中细菌复制的影响以及巨噬细胞对感染的免疫反应。此外，还确定了茶儿茶素的主要形式表没食子儿茶素没食子酸酯（EGCg）对CSC诱导的肺泡巨噬细胞抗菌活性抑制和免疫反应的可能免疫治疗作用。用CSC处理小鼠肺泡巨噬细胞系（MH-S）细胞显著增强了巨噬细胞中嗜肺军团菌的复制，并选择性下调了由细菌感染诱导的白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α）的产生。用EGCg处理巨噬细胞不仅克服了CSC诱导的抗菌活性抑制，还增强了巨噬细胞对感染的抵抗力。EGCg还显著上调了CSC抑制的巨噬细胞在感染时IL-6和TNF-α的产生。外源性TNF-α处理以及用抗TNF-α和抗γ-干扰素（IFN-γ）抗体进行中和处理的结果以及IFN-γ mRNA水平的测定表明，CSC抑制的巨噬细胞可被EGCg激活，通过上调TNF-α和IFN-γ的产生来抑制嗜肺军团菌的生长。因此，本研究表明CSC选择性地改变巨噬细胞对嗜肺军团菌感染的免疫反应，并导致巨噬细胞中细菌复制增强。此外，茶儿茶素EGCg可以减轻CSC对肺泡巨噬细胞的这种抑制作用。
