Lloyd Clare M, Rankin Sara M
Leukocyte Biology, Biomedical Sciences Division, Faculty of Medicine, South Kensington Campus, Imperial College, London SW7 2AZ, UK.
Curr Opin Pharmacol. 2003 Aug;3(4):443-8. doi: 10.1016/s1471-4892(03)00069-9.
Expression of chemokine receptors on T helper 2 cells and eosinophils has been postulated to be the mechanism by which these cells are selectively recruited to the lung during allergic inflammatory reactions. Mouse models have provided evidence to show that blocking the ligands for these receptors is successful in abrogating the pathophysiological effects of allergen challenge. However, recent studies describing the effect of genetic deletions of these chemokine receptors have not confirmed the results obtained with ligand knockouts or neutralising antibodies. Coupled with the realisation that, because of a lack of species cross-reactivity, it is not possible to test small molecule antagonists against human receptors in the original in vivo animal models, the future of chemokine receptor therapeutics is in question. However, recent advances have been made regarding the therapeutic potential of blocking the chemokine receptors CCR3, CCR4 and CCR8 in allergic airway disease.
趋化因子受体在辅助性T细胞2型细胞和嗜酸性粒细胞上的表达被认为是在变应性炎症反应期间这些细胞被选择性募集到肺的机制。小鼠模型已提供证据表明，阻断这些受体的配体可成功消除变应原激发的病理生理效应。然而，最近描述这些趋化因子受体基因缺失效应的研究并未证实配体敲除或中和抗体所获得的结果。再加上由于缺乏种间交叉反应性，无法在原始体内动物模型中针对人类受体测试小分子拮抗剂，趋化因子受体疗法的未来受到质疑。然而，在变应性气道疾病中，关于阻断趋化因子受体CCR3、CCR4和CCR8的治疗潜力已取得了最新进展。
