Expression of secretory group IIA phospholipase A(2) in relation to the presence of microbial agents, macrophage infiltrates, and transcripts of proinflammatory cytokines in human aortic tissues.

Recent seroepidemiological and immunohistochemical studies have demonstrated an association between microbial infections and atherosclerosis. However, the mechanisms underlying this association are widely unknown. In the present study, arterial specimens obtained at autopsy after sudden death were analyzed concerning (1) the presence of Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori; (2) the expression of secretory group IIA phospholipase A(2) (sPLA(2)-IIA) and of proinflammatory cytokines; and (3) the stage of atherosclerosis. Genomic DNA of microbial pathogens was determined by the polymerase chain reaction technique. The expression of sPLA(2)-IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA(2)-IIA. Transcripts specific for sPLA(2)-IIA, interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were identified by reverse transcription-polymerase chain reaction. In 18 of 102 analyzed specimens, DNA of microbial pathogens was found. Thirteen sections were positive for C pneumoniae, whereas 2 specimens were positive either for cytomegalovirus or for herpes simplex virus. One section contained genomic DNA of all 3 pathogens simultaneously. None of the analyzed tissues exhibited nucleic acids specific for H pylori. In addition to macrophage infiltrates, the presence of microbial DNA was closely associated with the occurrence of transcripts specific for proinflammatory cytokines and sPLA(2)-IIA. Pathogens as well as sPLA(2)-IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA(2)-IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A(2)-treated lipoproteins are transformed into foam cells in vitro, the results of this study suggest an alternative mechanism by which microbial infections may act in a proatherogenic fashion in vessel walls.

近期的血清流行病学和免疫组织化学研究表明微生物感染与动脉粥样硬化之间存在关联。然而，这种关联背后的机制在很大程度上尚不明确。在本研究中，对猝死尸检所获得的动脉标本进行了分析，涉及以下方面：（1）肺炎衣原体、巨细胞病毒、单纯疱疹病毒和幽门螺杆菌的存在情况；（2）分泌型IIA族磷脂酶A(2)（sPLA(2)-IIA）和促炎细胞因子的表达；（3）动脉粥样硬化的阶段。微生物病原体的基因组DNA通过聚合酶链反应技术测定。使用针对人sPLA(2)-IIA的单克隆抗体通过免疫组织化学方法研究sPLA(2)-IIA的表达。通过逆转录 - 聚合酶链反应鉴定sPLA(2)-IIA、白细胞介素 - 1β、肿瘤坏死因子 - α和干扰素 - γ的特异性转录本。在分析的102个标本中，有18个发现了微生物病原体的DNA。13个切片肺炎衣原体呈阳性，而2个标本分别巨细胞病毒或单纯疱疹病毒呈阳性。一个切片同时含有所有3种病原体的基因组DNA。分析的组织中均未显示幽门螺杆菌特异性核酸。除了巨噬细胞浸润外，微生物DNA的存在与促炎细胞因子和sPLA(2)-IIA特异性转录本的出现密切相关。发现病原体以及sPLA(2)-IIA和细胞因子不仅存在于动脉粥样硬化的晚期，也存在于早期阶段。在sPLA(2)-IIA和细胞因子表达阴性的组织中，未发现任何病原体。因为在体外，暴露于磷脂酶A(2)处理的脂蛋白的巨噬细胞会转化为泡沫细胞，所以本研究结果提示了一种微生物感染在血管壁中可能以促动脉粥样硬化方式起作用的替代机制。