Qi Mingshan, Miyakawa Hiroshi, Kuramitsu Howard K
Department of Oral Biology, State University of New York, 3435 Main Street, Buffalo 14214-3092, NY, USA.
Microb Pathog. 2003 Dec;35(6):259-67. doi: 10.1016/j.micpath.2003.07.002.
Atherosclerosis is a complex pathologic process initialed by the formation of cholesterol-rich plaque. Macrophages play a central role in the development of atherosclerosis, specifically in the initial accumulation of cholesterol in the arterial wall. It has been suggested that infection and chronic inflammatory conditions such as periodontitis may influence the atherosclerosis process. Porphyromonas gingivalis, one of the major pathogens involved in periodontitis, has been detected in human atheromas, suggesting that P. gingivalis infection may be associated with atherosclerosis. However, a causal relationship between this pathogen and the disease process has not yet been established. The purpose of the present investigation was to determine whether P. gingivalis could induce macrophages to form foam cells using the murine macrophage cell line (J774) as a model system. For inocula smaller than one bacterium per ten cells, P. gingivalis 381, as well as its lipopolysaccharide (LPS), induced foam cell formation of macrophages when cultured in the presence of human low-density lipoprotein (LDL). Infection of macrophages with increasing doses of P. gingivalis resulted in higher levels of foam cell formation. More than 70% of the cultured macrophages form cholesterol ester droplet-rich cells in the presence of 100 mug/ml of LDL when the inocula was more than 10 bacteria per cell. Low concentrations of P. gingivalis outer membrane vesicles also induced foam cell formation in the presence of LDL. In addition, it was demonstrated that P. gingivalis LPS alone was able to induce macrophage foam cell formation. P. gingivalis and its vesicles not only promoted LDL binding to macrophages but also induced macrophages to modify native LDL, which plays an important role in foam cell formation and the pathogenesis of atherosclerosis. Therefore, P. gingivalis cells or its vesicles released from periodontal lesions into the circulation may deliver virulence factor(s) such as LPS to the arterial wall to initiate or promote foam cell formation in macrophages and contribute to atheroma development.
动脉粥样硬化是一个由富含胆固醇的斑块形成引发的复杂病理过程。巨噬细胞在动脉粥样硬化的发展中起核心作用，特别是在动脉壁中胆固醇的初始蓄积方面。有人提出感染和诸如牙周炎等慢性炎症状况可能影响动脉粥样硬化进程。牙龈卟啉单胞菌是参与牙周炎的主要病原体之一，已在人类动脉粥样硬化斑块中检测到，这表明牙龈卟啉单胞菌感染可能与动脉粥样硬化有关。然而，这种病原体与疾病进程之间的因果关系尚未确立。本研究的目的是使用小鼠巨噬细胞系（J774）作为模型系统，确定牙龈卟啉单胞菌是否能诱导巨噬细胞形成泡沫细胞。对于每十个细胞接种量小于一个细菌的情况，牙龈卟啉单胞菌381及其脂多糖（LPS）在人低密度脂蛋白（LDL）存在下培养时，可诱导巨噬细胞形成泡沫细胞。用递增剂量的牙龈卟啉单胞菌感染巨噬细胞会导致更高水平的泡沫细胞形成。当接种量为每个细胞超过10个细菌时，在100微克/毫升LDL存在下，超过70%的培养巨噬细胞形成富含胆固醇酯滴的细胞。低浓度的牙龈卟啉单胞菌外膜囊泡在LDL存在下也能诱导泡沫细胞形成。此外，已证明单独的牙龈卟啉单胞菌LPS就能诱导巨噬细胞泡沫细胞形成。牙龈卟啉单胞菌及其囊泡不仅促进LDL与巨噬细胞的结合，还诱导巨噬细胞修饰天然LDL，这在泡沫细胞形成和动脉粥样硬化发病机制中起重要作用。因此，从牙周病变释放到循环中的牙龈卟啉单胞菌细胞或其囊泡可能将诸如LPS等毒力因子传递到动脉壁，以启动或促进巨噬细胞中泡沫细胞的形成，并有助于动脉粥样硬化斑块的发展。
