Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Koshien, Nishinomiya, Hyogo 663-8179, Japan.
Immunol Lett. 2010 Jan 18;128(1):74-9. doi: 10.1016/j.imlet.2009.11.007. Epub 2009 Nov 24.
We investigated IgE-mediated allergic responses in a metabolic syndrome model rat strain, SHRSP.Z, which develops obesity and hypertension to cast light on the relationship between metabolic disturbances and allergic responses. IgE-mediated cutaneous anaphylactic responses were severely attenuated in this strain regardless of the presence of fa/fa mutation, compared with the parental WKY/Izm strain. Furthermore, in the peritoneal mast cells of both the SHRSP.Z and SHRSP/Izm strains, IgE-mediated activation, such as degranulation and protein tyrosine phosphorylation, was severely impaired whereas no significant differences were found in morphology and number of peritoneal mast cells. Immunoblot analyses revealed that phosphorylation levels of Syk upon IgE-mediated antigen stimulation were significantly decreased and basal expression of linker for activation of T cells (LAT) was down-regulated in peritoneal mast cells of the SHRSP strains. These results suggest that attenuated cutaneous allergic responses in the SHRSP.Z strain might be attributed to impaired FcvarepsilonRI-mediated signal transduction in mast cells.
我们研究了代谢综合征模型大鼠品系 SHRSP.Z 中的 IgE 介导的过敏反应,该品系发展为肥胖和高血压,以阐明代谢紊乱与过敏反应之间的关系。与亲本 WKY/Izm 品系相比,无论是否存在 fa/fa 突变,该品系的 IgE 介导的皮肤过敏反应均明显减弱。此外,在 SHRSP.Z 和 SHRSP/Izm 两种品系的腹腔肥大细胞中,IgE 介导的活化,如脱颗粒和蛋白酪氨酸磷酸化,严重受损,而腹腔肥大细胞的形态和数量无明显差异。免疫印迹分析显示,在 IgE 介导的抗原刺激下,SHRSP 品系腹腔肥大细胞中 Syk 的磷酸化水平显著降低,激活 T 细胞的衔接蛋白(LAT)的基础表达下调。这些结果表明,SHRSP.Z 品系皮肤过敏反应减弱可能归因于肥大细胞中 FcεRI 介导的信号转导受损。