Research and Development, Bristol-Myers Squibb, Princeton, New Jersey 08543, USA.
J Leukoc Biol. 2010 Jul;88(1):41-55. doi: 10.1189/jlb.1009671. Epub 2010 Apr 1.
A cardinal feature of inflammation is the tissue recruitment of leukocytes, a process that is mediated predominantly by chemokines via their receptors on migrating cells. CCR2 and CCR5, two CC chemokine receptors, are important players in the trafficking of monocytes/macrophages and in the functions of other cell types relevant to disease pathogenesis. This review provides a brief overview of the biological actions of CCR2 and CCR5 and a comprehensive summary of published data that demonstrate the involvement of both receptors in the pathogenesis of immunologic diseases (RA, CD, and transplant rejection) and cardiovascular diseases (atherosclerosis and AIH). In light of the potential for functional redundancy of chemokine receptors in mediating leukocyte trafficking and the consequent concern over insufficient efficacy offered by pharmacologically inhibiting one receptor, this review presents evidence supporting dual targeting of CCR2 and CCR5 as a more efficacious strategy than targeting either receptor alone. It also examines potential safety issues associated with such dual targeting.
炎症的一个主要特征是白细胞向组织募集，这一过程主要通过趋化因子及其在迁移细胞上的受体来介导。CCR2 和 CCR5 是两种 CC 趋化因子受体，它们在单核细胞/巨噬细胞的迁移和与疾病发病机制相关的其他细胞类型的功能中起着重要作用。这篇综述简要概述了 CCR2 和 CCR5 的生物学作用，并全面总结了已发表的数据，这些数据表明这两种受体都参与了免疫性疾病（RA、CD 和移植排斥）和心血管疾病（动脉粥样硬化和 AIH）的发病机制。鉴于趋化因子受体在介导白细胞迁移中的功能冗余的可能性，以及药理学抑制一种受体所带来的疗效不足的担忧，本综述提供了支持双重靶向 CCR2 和 CCR5 作为比单独靶向一种受体更有效的策略的证据。它还研究了与这种双重靶向相关的潜在安全问题。
