Ashida Kazuhiro, Miyazaki Koji, Takayama Eiji, Tsujimoto Hironori, Ayaori Makoto, Yakushiji Tadayuki, Iwamoto Noriyuki, Yonemura Astushi, Isoda Kikuo, Mochizuki Hidetaka, Hiraide Hoshio, Kusuhara Masatoshi, Ohsuzu Fumitaka
Internal Medicine I, National Defense Medical College, Saitama, Japan.
J Atheroscler Thromb. 2005;12(1):53-60. doi: 10.5551/jat.12.53.
TLRs are receptors involved in the recognition of pathogens by the innate immune system, and TLR2 and TLR4 play important roles in the activation of monocytes. A total of 105 consecutive patients who underwent coronary angiography comprised of 46 with stable effort angina (SA), 41 with unstable angina (UA), and 18 with no significant CAD (CNT) were enrolled. The baseline expression levels of TLR2 and TLR4 on monocytes in peripheral blood mononuclear cells (PBMCs) were determined by flow-cytometric analysis. Since TLR2 expression has been reported to be regulated by TLR4 signaling, we cultured PBMCs with or without lipopolysaccharide (LPS, 1 microg/ml). At baseline, TLR4 levels (mean of fluorescence intensity ) in SA (145 +/- 58, p < 0.05) and UA (164 +/- 65, p < 0.01) were higher than those in CNT (107 +/- 37). As for TLR2, levels were higher in UA (108 +/- 36, p < 0.05) than in SA (94 +/- 18) and CNT (87 +/- 22). After stimulation with LPS, TLR2 levels increased in SA but decreased in UA. In conclusions, TLR4 levels increased in both SA and UA. Monocytes in UA were characterized by elevated TLR2 levels and unresponsiveness of the TLR2 levels to TLR4 stimulation.
Toll样受体(TLRs)是先天性免疫系统中参与识别病原体的受体,TLR2和TLR4在单核细胞激活中起重要作用。连续纳入105例接受冠状动脉造影的患者,其中46例为稳定型劳力性心绞痛(SA),41例为不稳定型心绞痛(UA),18例无显著冠状动脉疾病(CNT)。通过流式细胞术分析测定外周血单个核细胞(PBMCs)中单核细胞上TLR2和TLR4的基线表达水平。由于据报道TLR2表达受TLR4信号调节,我们用或不用脂多糖(LPS,1微克/毫升)培养PBMCs。基线时,SA组(145±58,p<0.05)和UA组(164±65,p<0.01)的TLR4水平(平均荧光强度)高于CNT组(107±37)。至于TLR2,UA组(108±36,p<0.05)的水平高于SA组(94±18)和CNT组(87±22)。用LPS刺激后,SA组的TLR2水平升高,而UA组降低。总之,SA和UA组的TLR4水平均升高。UA组单核细胞的特征是TLR2水平升高且TLR2水平对TLR4刺激无反应。