Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, Campus de Cantoblanco, Madrid E-28049, Spain.
Immunol Lett. 2012 Jul 30;145(1-2):23-9. doi: 10.1016/j.imlet.2012.04.012.
A broad array of biological responses including cell polarization, movement, immune and inflammatory responses, as well as prevention of HIV-1 infection, are triggered by the chemokines, a family of secreted and structurally related chemoattractant proteins that bind to class A-specific seven-transmembrane receptors linked to G proteins. Chemokines and their receptors should not be considered isolated entities, as they act in complex networks. Chemokines bind as oligomers, or oligomerize after binding to glycosaminoglycans on endothelial cells, and are then presented to their receptors on target cells, facilitating the generation of chemoattractant gradients. The chemokine receptors form homo- and heterodimers, as well as higher order structures at the cell surface. These structures are dynamic and are regulated by receptor expression and ligand levels. Complexity is even greater, as in addition to regulation by cytokines and decoy receptors, chemokine and receptor levels are affected by proteolytic cleavage and other protein modifications. This complex scenario should be considered when analyzing chemokine biology and the ability of their antagonists to act in vivo. Strategies based on blocking or stabilizing ligand and receptor dimers could be alternative approaches that might have broad therapeutic potential.
趋化因子是一大类分泌型结构相关趋化因子蛋白，能够与 A 类特异性七跨膜受体（与 G 蛋白偶联）结合，从而引发广泛的生物学反应，包括细胞极化、运动、免疫和炎症反应，以及预防 HIV-1 感染。趋化因子及其受体不应被视为孤立的实体，因为它们在复杂的网络中发挥作用。趋化因子以寡聚体结合，或者在与内皮细胞上的糖胺聚糖结合后寡聚化，然后呈递给靶细胞上的受体，促进趋化因子梯度的产生。趋化因子受体在细胞表面形成同型和异型二聚体以及更高阶结构。这些结构是动态的，并受受体表达和配体水平的调节。更复杂的是，除了受细胞因子和诱饵受体的调节外，趋化因子和受体的水平还受到蛋白水解切割和其他蛋白修饰的影响。在分析趋化因子生物学及其拮抗剂在体内的作用时，应考虑到这种复杂的情况。基于阻断或稳定配体和受体二聚体的策略可能是具有广泛治疗潜力的替代方法。
