Elsner J, Petering H, Kimmig D, Wells T N, Proudfoot A E, Kapp A
Department of Dermatology, Hannover Medical School, Hannover, Germany.
Int Arch Allergy Immunol. 1999 Feb-Apr;118(2-4):462-5. doi: 10.1159/000024164.
Eosinophils play an important role in allergic diseases such as allergic asthma, rhinoconjunctivitis and atopic dermatitis. Recruitement of eosinophils to the side of inflammation, the release of reactive oxygen species, leading to tissue damage, and the propagation of the inflammatory response are mediated by chemokines. Thus, the applicability of agents able to inhibit or antagonize chemokine-induced eosinophil activation seems to be of interest in the treatment of allergic diseases. Therefore, the effect of the CC chemokine antagonist, Met-RANTES, on its effect on human eosinophil effector functions in response to RANTES, MCP-3 and eotaxin was investigated. Met-RANTES had no intrinsic activity on [Ca2+]i transients in eosinophils and was able to dose-dependently inhibit [Ca2+]i transients in eosinophils following stimulation with RANTES, MCP-3 and eotaxin. Besides its effect on [Ca2+]i transients, Met-RANTES dose-dependently inhibited actin polymerization in eosinophils and the release of reactive oxygen species following stimulation with RANTES, MCP-3 and eotaxin. The results of this study lead to the conclusion that Met-RANTES is an effective and powerful compound to antagonize effector functions of human eosinophils following stimulation with RANTES, MCP-3 and eotaxin and is therefore a promising therapeutic approach to prevent the invasion and destructive power of eosinophils in allergic diseases.
嗜酸性粒细胞在过敏性疾病如过敏性哮喘、鼻结膜炎和特应性皮炎中发挥着重要作用。趋化因子介导嗜酸性粒细胞向炎症部位募集、活性氧的释放（导致组织损伤）以及炎症反应的传播。因此，能够抑制或拮抗趋化因子诱导的嗜酸性粒细胞活化的药物在过敏性疾病治疗中似乎具有应用价值。因此，研究了CC趋化因子拮抗剂Met-RANTES对其在响应RANTES、MCP-3和嗜酸性粒细胞趋化因子时对人嗜酸性粒细胞效应功能的影响。Met-RANTES对嗜酸性粒细胞中[Ca2+]i瞬变无内在活性，并且能够剂量依赖性地抑制RANTES、MCP-3和嗜酸性粒细胞趋化因子刺激后嗜酸性粒细胞中的[Ca2+]i瞬变。除了对[Ca2+]i瞬变的影响外，Met-RANTES还剂量依赖性地抑制RANTES、MCP-3和嗜酸性粒细胞趋化因子刺激后嗜酸性粒细胞中的肌动蛋白聚合和活性氧的释放。本研究结果得出结论，Met-RANTES是一种有效且强大的化合物，可拮抗RANTES、MCP-3和嗜酸性粒细胞趋化因子刺激后人嗜酸性粒细胞的效应功能，因此是预防嗜酸性粒细胞在过敏性疾病中侵袭和破坏能力的一种有前景的治疗方法。
