Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Taejon, 301-746, Republic of Korea.
Mol Biol Rep. 2013 Oct;40(10):5875-81. doi: 10.1007/s11033-013-2695-z. Epub 2013 Sep 25.
We investigated the effect of asthmatic serum on constitutive eosinophil apoptosis in normal subjects. Eosinophil apoptosis in normal subjects was inhibited by asthmatic serum but not normal serum. In a detailed analysis based on the presence of house dust mite (HDM) IgE, HDM IgE-positive (+) asthmatic serum was more effective for eosinophil apoptosis than that of HDM IgE-negative (-) asthmatic serum. HDM IgE+ asthmatic serum inhibited both HDM IgE- and HDM IgE+ normal eosinophil apoptosis, and HDM IgE- asthmatic serum suppressed eosinophil apoptosis of HDM IgE+ normal. HDM IgE- normal serum did not inhibit either HDM IgE- or HDM IgE+ normal eosinophil apoptosis, and HDM IgE+ normal serum inhibited HDM IgE+ normal eosinophil apoptosis. The kind of HDM IgE (Dermatophagoides pteronissinus-specific IgE and Dermatophagoides farinae-specific IgE) was not related to the effect of asthmatic serum on eosinophil apoptosis. Extracts of DP and DF, Der p1, and Der p2, were not effective for eosinophil apoptosis. HDM IgE+ asthmatic serum inhibited cleavage of procaspase 9 and procaspase 3. Asthmatic serum induced Akt and ERK phosphorylation, and ERK activation was suppressed by AKTi. Taken together, asthmatic serum inhibited normal eosinophil apoptosis via PI3K/Akt/ERK cascade. The novel approach taken in this study provided better insight into HDM-associated anti-apoptotic mechanism of eosinophils in patients with asthma.
我们研究了哮喘患者血清对正常个体嗜酸性粒细胞凋亡的影响。哮喘患者血清可抑制正常个体嗜酸性粒细胞凋亡，而正常血清则无此作用。基于屋尘螨（HDM）IgE 的存在进行详细分析后发现，HDM IgE 阳性（+）哮喘患者血清比 HDM IgE 阴性（-）哮喘患者血清更能有效抑制嗜酸性粒细胞凋亡。HDM IgE+哮喘患者血清可抑制 HDM IgE-和 HDM IgE+正常嗜酸性粒细胞凋亡，而 HDM IgE-哮喘患者血清则抑制 HDM IgE+正常嗜酸性粒细胞凋亡。HDM IgE-正常血清对 HDM IgE-和 HDM IgE+正常嗜酸性粒细胞凋亡均无抑制作用，而 HDM IgE+正常血清则抑制 HDM IgE+正常嗜酸性粒细胞凋亡。HDM IgE 的种类（屋尘螨特异性 IgE1 和屋尘螨特异性 IgE2）与哮喘患者血清对嗜酸性粒细胞凋亡的影响无关。DP 和 DF 的提取物、Der p1 和 Der p2 对嗜酸性粒细胞凋亡均无作用。HDM IgE+哮喘患者血清可抑制前半胱氨酸天冬氨酸蛋白酶 9 和前半胱氨酸天冬氨酸蛋白酶 3 的切割。哮喘患者血清可诱导 Akt 和 ERK 磷酸化，而 ERK 激活可被 AKTi 抑制。综上所述，哮喘患者血清通过 PI3K/Akt/ERK 级联抑制正常嗜酸性粒细胞凋亡。本研究采用的新方法使我们对哮喘患者中 HDM 相关嗜酸性粒细胞抗凋亡机制有了更好的了解。
