Scavuzzo M, Sagripanti A, Mosca F, Ambrogi F
Dept. Internal Medicine, S. Chiara Hospital, Pisa, Italy.
Biomed Pharmacother. 2001 Feb;55(1):61-9. doi: 10.1016/s0753-3322(00)00012-3.
Cyclosporine (CsA) is an immunosuppressive drug widely used to prevent allograft rejection, but its action on neutrophil function is not well known. Neutrophils play an important role in tissue damage during allograft rejection; chemotactic recruitment, adhesion to endothelial cells and oxidative burst of neutrophils are early events during allograft rejection. The aim of this work was to evaluate the effect of CsA on beta2 integrins' surface expression, adhesion to human umbilical endothelial cells (HUVECs), chemotaxis and oxidative burst by neutrophils. For any neutrophil function studied, data obtained from activated neutrophils exposed to CsA were compared with those derived from untreated controls. Results show that CsA does not block neutrophil chemotaxis and does not reduce surface expression of CD11 complex and HUVECs' adhesion at all concentrations tested (15, 100 and 500 ng/mL) and at incubation times of 1, 2 and 4 h as compared to controls. On the other hand, the drug affects significantly the CD18 phenotype after two hours of treatment at the maximum concentration (500 ng/mL) (P < 0.05; ANOVA) and the oxidative burst after four hours (P < 0.01; ANOVA). This study provides evidence that in addition to the well-known CsA effects on lymphocyte functions, the drug affects some neutrophil functions with dose- and time-dependent modalities.
环孢素（CsA）是一种广泛用于预防同种异体移植排斥反应的免疫抑制药物，但其对中性粒细胞功能的作用尚不明确。中性粒细胞在同种异体移植排斥反应所致的组织损伤中起重要作用；中性粒细胞的趋化募集、与内皮细胞的黏附以及氧化爆发是同种异体移植排斥反应早期的事件。本研究旨在评估环孢素对β2整合素的表面表达、与人类脐静脉内皮细胞（HUVECs）的黏附、趋化性以及中性粒细胞氧化爆发的影响。对于所研究的任何中性粒细胞功能，将暴露于环孢素的活化中性粒细胞所获得的数据与未处理对照组的数据进行比较。结果显示，与对照组相比，在所有测试浓度（15、100和500 ng/mL）以及1、2和4小时的孵育时间下，环孢素均不阻断中性粒细胞趋化性，也不降低CD11复合物的表面表达和HUVECs的黏附。另一方面，在最大浓度（500 ng/mL）处理两小时后，该药物对CD18表型有显著影响（P < 0.05；方差分析），在四小时后对氧化爆发有显著影响（P < 0.01；方差分析）。本研究提供了证据，表明除了环孢素对淋巴细胞功能的已知作用外，该药物还以剂量和时间依赖性方式影响一些中性粒细胞功能。
