Kalayoglu M V, Perkins B N, Byrne G I
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, 436 SMI, 1300 University Avenue, Madison, WI 53706, USA.
Microbes Infect. 2001 Oct;3(12):963-9. doi: 10.1016/s1286-4579(01)01458-7.
Interactions between monocytes and endothelial cells play an important role in the pathogenesis of atherosclerosis, and monocyte adhesion to arterial endothelium is one of the earliest events in atherogenesis. Work presented in this study examined human monocyte adherence to primary human aortic endothelial cells following monocyte infection with Chlamydia pneumoniae, an intracellular pathogen associated with atherosclerosis by a variety of sero-epidemiological, pathological and functional studies. Infected monocytes exhibited enhanced adhesion to aortic endothelial cells in a time- and dose-dependent manner. Pre-treatment of C. pneumoniae with heat did not effect the organism's capacity to enhance monocyte adhesion, suggesting that heat-stable chlamydial antigens such as chlamydial lipopolysaccharide (cLPS) mediated monocyte adherence. Indeed, treatment of monocytes with cLPS was sufficient to increase monocyte adherence to endothelial cells, and increased adherence of infected or cLPS-treated monocytes could be inhibited by the LPS antagonist lipid X. Moreover, C. pneumoniae-induced adherence could be inhibited by incubating monocytes with a mAb specific to the human beta 2-integrin chain, suggesting that enhanced adherence resulted from increased expression of these adhesion molecules. These data show that C. pneumoniae can enhance the capacity of monocytes to adhere to primary human aortic endothelial cells. The enhanced adherence exhibited by infected monocytes may increase monocyte residence time in vascular sites with reduced wall shear stress and promote entry of infected cells into lesion-prone locations.
单核细胞与内皮细胞之间的相互作用在动脉粥样硬化的发病机制中起着重要作用，单核细胞黏附于动脉内皮是动脉粥样硬化形成过程中最早出现的事件之一。本研究中的工作检测了肺炎衣原体感染单核细胞后，人单核细胞对原代人主动脉内皮细胞的黏附情况。通过各种血清流行病学、病理学和功能研究，肺炎衣原体这种细胞内病原体与动脉粥样硬化相关。受感染的单核细胞以时间和剂量依赖的方式表现出对主动脉内皮细胞黏附增强。用热预处理肺炎衣原体并不影响该病原体增强单核细胞黏附的能力，这表明热稳定的衣原体抗原如衣原体脂多糖（cLPS）介导了单核细胞的黏附。事实上，用cLPS处理单核细胞足以增加单核细胞对内皮细胞的黏附，并且感染或cLPS处理的单核细胞增加的黏附可被LPS拮抗剂脂质X抑制。此外，通过用针对人β2整合素链的单克隆抗体孵育单核细胞，可抑制肺炎衣原体诱导的黏附，这表明黏附增强是由于这些黏附分子表达增加所致。这些数据表明，肺炎衣原体可增强单核细胞对原代人主动脉内皮细胞的黏附能力。受感染的单核细胞表现出的增强黏附可能会增加单核细胞在壁剪切应力降低的血管部位的停留时间，并促进受感染细胞进入易发生病变的位置。
