Akutsu I, Fukuda T, Makino S
Department of Medicine and Clinical Immunology, Dokkyo University School of Medicine.
Arerugi. 1992 Jul;41(7):778-86.
We have previously reported that the 5-day culture supernatants of peripheral blood mononuclear cells (PBMC) from Dermatophagides farinae (DF) sensitive asthmatics stimulated with 10 ng/ml DF antigen contain eosinophil chemotactic activity (ECA) with an apparent molecular weight greater than 30000 Da. In the present study, we examined the effects of CyA and FK on the ECA. ECA was tested using modified Boyden chamber method. We found that when CyA or FK was added to the culture throughout the experiment, the production of the factors with ECA by PBMC was inhibited in a dose-dependent manner. These inhibitory effects were unchanged by the addition of a sufficient dose of IL-2 to the culture medium. Isoelectrofocusing of the PBMC culture supernatants consistently yielded a major ECF activity at pH 7.0-7.5. The addition of CyA inhibited this major peak. In conclusion, these results suggest that mononuclear cells stimulated with related antigen produce substances which possess ECA and that CyA and FK can block the production of this substance. Therefore, there is a possibility that an immunosuppressive agent may be useful in bronchial asthma therapy by inhibiting the migration of eosinophils.
我们之前报道过,来自粉尘螨(DF)敏感型哮喘患者的外周血单个核细胞(PBMC)经10 ng/ml DF抗原刺激后培养5天的上清液含有嗜酸性粒细胞趋化活性(ECA),其表观分子量大于30000 Da。在本研究中,我们检测了环孢素A(CyA)和他克莫司(FK)对ECA的影响。使用改良的Boyden小室法检测ECA。我们发现,若在整个实验过程中向培养物中添加CyA或FK,PBMC产生具有ECA的因子会受到剂量依赖性抑制。向培养基中添加足量的白细胞介素-2(IL-2)并不会改变这些抑制作用。对PBMC培养上清液进行等电聚焦,在pH 7.0 - 7.5时始终产生一个主要的嗜酸性粒细胞趋化因子(ECF)活性峰。添加CyA会抑制这个主要峰。总之,这些结果表明,经相关抗原刺激的单核细胞会产生具有ECA的物质,并且CyA和FK可阻断该物质的产生。因此,免疫抑制剂有可能通过抑制嗜酸性粒细胞的迁移而在支气管哮喘治疗中发挥作用。