Elsner J, Oppermann M, Kapp A
Hannover Medical School, Department of Dermatology, Germany.
Eur J Immunol. 1996 Jul;26(7):1560-4. doi: 10.1002/eji.1830260723.
Eosinophils and complement activation are reported to play a crucial role in the pathogenesis of connective tissue diseases. Depositions of antigens and antigen-antibody complexes lead to complement activation with the generation of anaphylatoxins, particularly C5a, which is thought to be responsible for the infiltration and activation of eosinophils in the tissue. Previous studies suggested that the eosinophil C5a receptor differs structurally from the receptor expressed on neutrophils. In this study, we investigated the expression and functional properties of C5a receptors on human eosinophils using the C5a receptor monoclonal antibody S5/1 (anti-CD88 mAb). Flow cytometric analysis demonstrated that the anti-CD88 mAb bound homogeneously on the surface of human eosinophils from nonatopic healthy donors. In addition, no subpopulations with respect to C5a receptor expression were identified in normodense or hypodense eosinophils of patients with hypereosinophilia. Pre-incubation of eosinophils with anti-CD88 specifically inhibited C5a-induced intracellular calcium concentration transients. C5a-induced chemotactic activity of eosinophils was significantly inhibited after pre-incubation of cells with anti-CD88 mAb in a dose-dependent manner. Furthermore, anti-CD88 mAb inhibited dose-dependently the release of reactive oxygen species by eosinophils following stimulation with C5a. Thus, the human eosinophil C5a receptor is homogeneously expressed on normal eosinophils from healthy donors as well as on hypodense and normodense eosinophil subpopulations from patients with hypereosinophilia. Based on the inhibitory effect of the S5/1 mAb on C5a-stimulated eosinophil effector functions, we conclude that a single C5a receptor type exists on human eosinophils. In addition, the inhibitory effect of the S5/1 mAb on C5a functions may enable a new experimental approach to the treatment of diseases that have been associated with C5a-mediated activation.
据报道，嗜酸性粒细胞和补体激活在结缔组织疾病的发病机制中起关键作用。抗原和抗原 - 抗体复合物的沉积导致补体激活并产生过敏毒素，特别是C5a，它被认为是组织中嗜酸性粒细胞浸润和激活的原因。先前的研究表明，嗜酸性粒细胞C5a受体在结构上与中性粒细胞上表达的受体不同。在本研究中，我们使用C5a受体单克隆抗体S5/1（抗CD88单克隆抗体）研究了人嗜酸性粒细胞上C5a受体的表达和功能特性。流式细胞术分析表明，抗CD88单克隆抗体均匀地结合在非特应性健康供体的人嗜酸性粒细胞表面。此外，在嗜酸性粒细胞增多症患者的正常密度或低密度嗜酸性粒细胞中未发现C5a受体表达的亚群。用抗CD88预孵育嗜酸性粒细胞可特异性抑制C5a诱导的细胞内钙浓度瞬变。在用抗CD88单克隆抗体预孵育细胞后呈剂量依赖性地显著抑制了C5a诱导的嗜酸性粒细胞趋化活性。此外，抗CD88单克隆抗体剂量依赖性地抑制了C5a刺激后嗜酸性粒细胞活性氧的释放。因此，人嗜酸性粒细胞C5a受体在健康供体的正常嗜酸性粒细胞以及嗜酸性粒细胞增多症患者的低密度和正常密度嗜酸性粒细胞亚群上均有均匀表达。基于S5/1单克隆抗体对C5a刺激的嗜酸性粒细胞效应功能的抑制作用，我们得出结论，人嗜酸性粒细胞上存在单一类型的C5a受体。此外，S5/1单克隆抗体对C5a功能的抑制作用可能为治疗与C5a介导的激活相关的疾病提供一种新的实验方法。
