Spisani S, Fabbri E, Muccinelli M, Cariani A, Barbin L, Trotta F, Dovigo L
Department of Biochemistry and Molecular Biology, University of Ferrara, Ferrara, Italy.
Rheumatology (Oxford). 2001 Jul;40(7):794-800. doi: 10.1093/rheumatology/40.7.794.
Cyclosporin A (CsA) is an effective agent in rheumatoid arthritis (RA), slowing joint damage progression. Its therapeutic effect on T lymphocytes has been studied extensively, but there is little information available about neutrophils, the cells responsible for a substantial proportion of inflammation. A study was performed to investigate the in vitro effects of CsA on neutrophil functions triggered by several agonists and determine whether the drug could counteract the binding of formyl-methionyl-leucyl-phenylalanine (fMLP) to its receptor and/or modulate changes in the intracellular Ca(2+) concentration ([Ca(2+)]i).
CsA was added to neutrophils 5-50 min before the incubation steps for neutrophil function assays (chemotaxis, superoxide anion production, lysozyme release), calcium measurements and receptor binding experiments.
CsA appeared to be particularly effective in lowering chemotaxis, superoxide anion production and lysozyme release induced by different agonists. However, it did not significantly affect either basal or agonist-stimulated neutrophil [Ca(2+)]i and the interaction between fMLP and its receptor.
Because of its in vitro inhibition of neutrophil functions, CsA appears to have considerable potential as an anti-inflammatory drug. Moreover, as it is also a potent immunosuppressive agent, it may reduce the progression of joint damage in RA. More work remains to be done to clarify the molecular mechanism of CsA action on neutrophils.
环孢素A（CsA）是类风湿关节炎（RA）的一种有效药物，可减缓关节损伤进展。其对T淋巴细胞的治疗作用已得到广泛研究，但关于中性粒细胞（在很大一部分炎症中起作用的细胞）的信息却很少。本研究旨在探讨CsA对几种激动剂触发的中性粒细胞功能的体外影响，并确定该药物是否能抵消甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）与其受体的结合及/或调节细胞内钙离子浓度（[Ca(2+)]i）的变化。
在进行中性粒细胞功能测定（趋化性、超氧阴离子产生、溶菌酶释放）、钙测量和受体结合实验的孵育步骤前5 - 50分钟，将CsA加入中性粒细胞中。
CsA似乎在降低不同激动剂诱导的趋化性、超氧阴离子产生和溶菌酶释放方面特别有效。然而，它对基础或激动剂刺激的中性粒细胞[Ca(2+)]i以及fMLP与其受体之间的相互作用均无显著影响。
由于其在体外对中性粒细胞功能的抑制作用，CsA似乎具有作为抗炎药物的巨大潜力。此外，由于它也是一种强效免疫抑制剂，它可能会减缓RA中关节损伤的进展。仍需开展更多工作以阐明CsA对中性粒细胞作用的分子机制。
