Peters W, Charo I F
Gladstone Institute of Cardiovascular Disease, and Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, California 94141-9100, USA.
Curr Opin Lipidol. 2001 Apr;12(2):175-80. doi: 10.1097/00041433-200104000-00011.
Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, but the signals that initiate their recruitment to the vessel wall are poorly understood. Here, we review in vivo studies in genetically altered mice that support the notion that monocyte chemoattractant protein-1 (a member of the chemokine family of chemotactic cytokines) and chemokine receptor 2 (its cognate receptor) play important roles in this recruitment. An unexpected finding in chemokine receptor 2-knockout mice was the diminished production of interferon-gamma, which is a potent macrophage activator. The basis of this cytokine defect is not yet clear, but suggests that chemokines may influence atherosclerotic lesion development at several levels. Understanding the roles of chemokines and cytokines in atherogenesis may provide a basis for the development of future therapeutic agents that are aimed at interrupting monocyte recruitment and activation.
血液单核细胞是富含脂质的泡沫细胞的前体，而泡沫细胞是早期动脉粥样硬化病变的标志，但启动它们募集至血管壁的信号却鲜为人知。在此，我们综述了对基因改造小鼠的体内研究，这些研究支持以下观点：单核细胞趋化蛋白-1（趋化细胞因子的趋化因子家族成员）和趋化因子受体2（其同源受体）在这一募集中发挥重要作用。趋化因子受体2基因敲除小鼠中的一个意外发现是γ干扰素（一种有效的巨噬细胞激活剂）的产生减少。这种细胞因子缺陷的基础尚不清楚，但表明趋化因子可能在多个层面影响动脉粥样硬化病变的发展。了解趋化因子和细胞因子在动脉粥样硬化发生中的作用，可能为开发旨在阻断单核细胞募集和激活的未来治疗药物提供基础。
