Dubertret L, Lebreton C
INSERM U 312, Service de Dermatologie, Hôpital Henri Mondor, Créteil.
Pathol Biol (Paris). 1987 Dec;35(10 Pt 2):1389-94.
A reproducible method for sequential study of migration out of human skin, phagocytosis and bactericidal activity of neutrophils is described. Untreated psoriatics exhibit an early increase of chemotactic activity (0-8 h, p less than 0.02) and subsequently a strong inhibition of chemotaxis (8-24 h, p less than 0.01), a slight decrease of phagocytosis and a decrease in bactericidal activity (20 mn, p less than 0.02; 30 mn, p less than 0.003); 60 mn, p less than 0.001; 120 mn, p less than 0.001) as compared with controls. After clearing of skin lesions, the early increased chemotactic activity returned to normal values but the subsequent chemotactic inhibition remains as strong as before treatment. Phagocytosis increased to normal values (p less than 0.02) and bactericidal activity also increased but remained significantly low. The abnormalities were more evident in migrating than in circulating neutrophils, underlining the sensitivity of the described method. Using the same method we have shown that the aromatic retinoid etretinate (Ro 10-9359) and its main metabolite (Ro 10-1670) significantly inhibit the migration of neutrophils from the blood to tissues when applied into skin chambers (0.1 mg/ml) or when given orally (1 mg/kg/day) for 8 days to normal volunteers. This pharmacological property could be closely linked to the antipsoriatic properties of these drugs.
本文描述了一种用于连续研究中性粒细胞从人皮肤中迁移、吞噬作用及杀菌活性的可重复方法。未经治疗的银屑病患者表现出趋化活性早期升高(0 - 8小时,p < 0.02),随后趋化作用受到强烈抑制(8 - 24小时,p < 0.01),吞噬作用略有下降,杀菌活性降低(20分钟,p < 0.02;30分钟,p < 0.003;60分钟,p < 0.001;120分钟,p < 0.001),与对照组相比。皮肤病变清除后,早期升高的趋化活性恢复到正常水平,但随后的趋化抑制仍与治疗前一样强烈。吞噬作用增加到正常水平(p < 0.02),杀菌活性也增加,但仍显著低于正常。这些异常在迁移的中性粒细胞中比在循环的中性粒细胞中更明显,突出了所描述方法的敏感性。使用相同的方法,我们已经表明,芳香维甲酸依曲替酯(Ro 10 - 9359)及其主要代谢产物(Ro 10 - 1670),当以0.1毫克/毫升的浓度应用于皮肤腔室或口服给予正常志愿者(1毫克/千克/天,持续8天)时,可显著抑制中性粒细胞从血液向组织的迁移。这种药理特性可能与这些药物的抗银屑病特性密切相关。