CRP诱导单核细胞表达CD11b和CCR2并影响脂蛋白对CD11b和CCR2表达的观察

目的探讨C反应蛋白(CRP)对单核细胞表达CC趋化因子受体2(CCR2)和CD11b的作用以及与脂蛋白之间的相互作用。方法以不同浓度的CRP和／或脂蛋白处理THP-1单核细胞,应用流式细胞仪检测细胞表面CCR2、CD11b蛋白的表达,并应用半定量RT-PCR方法检测CCR2的mRNA表达,同时检测处理后的单核细胞与内皮细胞的黏附率以及培养液中NO含量。结果CRP以剂量依赖性方式增加单核细胞表达CCR2和CD11b,RT-PCR结果显示CRP在转录水平上诱导CCR2的表达。不同脂蛋白对CCR2和CD11b的表达作用不同:氧化的低密度脂蛋白(OX-LDL)诱导CCR2和CD11b的表达(P<0．01),而高密度脂蛋白(HDL)抑制此二者的表达(P<0．01),天然低密度脂蛋白(LDL)则对其无显著影响(P<0．01)。CRP抑制OX-LDL所诱导的CCR2(115．7±6．40比99．0±3．65, P<0．01)和CD11b(121．3±4．79比98．5±4．90,P<0．01)的表达增加;但与LDL显著地协同上调CCR2(LDL 50μg/ml比LDL 50μg/ml+CRP 10μg／ml;CRP 10μg/ml比LDL 50μg/ml+CRP 10μg/ml,均P <0．01)和CD11b(LDL 50μg/ml比LDL 50μg/ml+CRP 10μg／ml;CRP 10μg／ml比LDL 50μg/ml+CRP 10μg/ml,均P<0．01)的表达;CRP削弱HDL对CCR2和CD11b表达的抑制作用。培养液中的NO含量与CCR2和CD11b密切相关。结论CRP诱导单核细胞表达CCR2和CD11b,并调节脂蛋白对CCR2和CD11b的作用;NO可能是此过程中的信使之一。

C-reactive protein modulates the effects of lipoproteins on expressions of CC chemokine receptor 2 and CD11b

Objective To investigate the effects of C-reactive protein(CRP) on expressions of CC che-mokine receptor 2(CCR2) and CD11b on monocyte, and the interactions between CRP and lipoproteins. Methods THP-1 monocytes were treated by CRP and/or lipoproteins of different concentrations. The protein expression of CCR2 and CD11b was measured by flow cytometry and mRNA expression of CCR2 was tested by RT-PCR. The number of monocytes adhering to endothelial cells and concentration of NO in supernatant were measured as well. Results CRP induced the protein expressions of CCR2 and CD11b on monocytes in a dose-dependent mode. lipoproteins had different effects on the expressions of CCR2 and CD11b: OX-LDL(oxidized low-density lipoprotein) induced the expressions(P<0.01), while HDL(high-density lipoprotein) induced inhibition of expression (P< 0.01). Native LDL(low-density lipoprotein) had no effect on them. CRP affected the roles of lipoprotein on CCR2 and CD11b. CRP synergetically upregulated CCR2; and CD11b expression with LDL, but down-regulated the increase efficacy of CCR2 induced by OX-LDL, when presented with CRP, the down-regulation effects of HDL on CCR2 and CD11b were inhibited. NO in culture medium was significantly related to CCR2 and CD11b. Conclusion CRP induces the expression of CCR2 and CD11b on the surface of monocytes and regulates the effects of lipoproteins on them. NO is a potential messenger in this course.