过氧化物酶体增殖剂激活受体α对小鼠T、B细胞发育的影响

Influence of the peroxisome proliferator-activated receptor alpha on the development of T and B cells in mice

目的研究过氧化物酶体增殖剂激活受体α(PPARα)与小鼠免疫系统功能和发育的关系。方法喂养含过氧化物酶体增殖剂(PP)的食物后,观察野生型C57Bl/6小鼠和PPARα缺陷型小鼠胸腺、脾脏的重量及胸腺细胞、脾细胞数量的变化。用抗小鼠CD3、CD4、CD8a、CD19、IgM或CD45R/220单克隆抗体(mAb)进行细胞免疫荧光染色后,用流式细胞术分析骨髓细胞、胸腺细胞和脾细胞的表型变化。用刀豆蛋白A(ConA)和脂多糖(LPS)分别刺激小鼠的脾细胞,用3H-TdR掺入法检测淋巴细胞增殖活性的变化。用RT-PCR检测小鼠骨髓、胸腺和脾脏中PPARαmRNA的表达。结果与野生型小鼠相比较,PP对PPARα缺陷型小鼠胸腺、脾脏的重量和细胞数,以及ConA和LPS刺激对淋巴细胞增殖反应的影响很小。PP可致野生型小鼠胸腺中CD4+CD8+T细胞数,骨髓中B220+B细胞总数和原/前B细胞数明显减少,但对PPARα缺陷型小鼠的上述T、B细胞亚群无显著影响。PPARαmRNA在小鼠胸腺和脾脏中呈低表达,在骨髓中不表达。结论PPARα在PP诱导的免疫调节中起主要作用,其可通过间接途径影响T、B细胞的发育。

AIM. To investigate the role of peroxisome proliferator-activated receptor a （PPARa） in the function and development of mouse immune system. METHODS： Wild-type and PPARa-null C57B/6 mice were sacrificed after 7-day dietary treatment of with peroxisome proliferator （PP）. The changes in the weight of the thymus and spleen and cell numbers from the thymus and spleen were observed. The alterations of the cell phenotypes in bone marrow, thymus and spleen were determined by immunofluorescent staining using anti-mouse CD3, CD4, CD8a, CD19, IgM or CD45R/220 mAb through FACS analysis. The proliferation of T or B cells in response to ConA or LPS, respectively, was analyzed by 3H-TdR labeling. The PPARa mRNA expression in the bone marrow, thymus and spleen was examined by RT-PCR. RESULTS： PP treatment caused significant decreases in the weight and cell numbers of thymus and spleen and proliferative responsiveness of lymphocytes to ConA and LPS in wild-type mice, whereas these effects were significantly weak in PPARα-null mice. The significant decreases of the CD4^＋ CD8^＋ population in the thymus and pro/pre-B cells and total B220^＋ cells in the bone marrow of wild-type mice with PP treatment, but not in PPARa-null mice. Interestingly, PPARα expression was detected in mouse thymus and spleen, rather than bone marrow. CONCLUSION： PPARα plays a major role in the PP-induced immunomodulation, indirectly affecting the development of T and B cells.