Wajner M, Santos K D, Schlottfeldt J L, Rocha M P, Wannmacher C M
Medical Genetics Unit, Hospital de Cl approximately ínicas de Porto Alegre, Rua Ramiro Barcelos 2600, CEP 90035-003, UFRGS Porto Alegre, RS, Brazil.
Clin Sci (Lond). 1999 Jan;96(1):99-103.
Recurrent infections are common features in patients affected by propionic acidaemia (McKusick 232000) and methylmalonic acidaemia (McKusick 251000). Since these disorders are biochemically characterized by tissue accumulation of propionic acid and methylmalonic acid respectively, it is possible that these compounds may act as immunosuppressants. We therefore investigated the effect of propionate and methylmalonate on cellular growth of human peripheral lymphocytes stimulated in vitro by phytohaemagglutinin, concanavalin A and pokeweed mitogen, a recognized test of cellular immunocompetence. Lymphocytes were cultured in flat-bottomed 96-well microplates at 37 degrees C for 96 h (phytohaemagglutinin and concanavalin A) or 144 h (pokeweed mitogen) in the presence of one mitogen at different concentrations and of one acid added at doses of 1.0, 2.5 or 5.0 mM. Cell blastogenesis was measured by the incorporation of tritiated thymidine into cellular DNA and compared with that of identical cultures with no acid added (controls). A consistent and progressive inhibitory effect of propionic acid with increasing concentrations in culture was identified with all mitogens and was more pronounced with pokeweed mitogen. Lymphocyte blastogenesis was not altered in the presence of methylmalonic acid. The effect of propionate was observed only when the drug was added at the beginning (phytohaemagglutinin-activated) or until 24 h (concanavalin A- and pokeweed mitogen-activated) of culture. The viability of lymphocytes after treatment with the drug, as assessed by the Trypan Blue exclusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity. In conclusion, propionic acid, which accumulates in tissues of patients with propionic acidaemia, causes 'in vitro' immunosuppression, which may be related to the recurrent infections characteristic of these patients.
反复感染是丙酸血症（麦库西克编号232000）和甲基丙二酸血症（麦库西克编号251000）患者的常见特征。由于这些疾病在生化方面分别以丙酸和甲基丙二酸在组织中的蓄积为特征，因此这些化合物有可能作为免疫抑制剂发挥作用。因此，我们研究了丙酸盐和甲基丙二酸盐对体外由植物血凝素、伴刀豆球蛋白A和商陆有丝分裂原刺激的人外周淋巴细胞细胞生长的影响，这是一种公认的细胞免疫能力测试。淋巴细胞在平底96孔微孔板中于37℃培养96小时（植物血凝素和伴刀豆球蛋白A）或144小时（商陆有丝分裂原），培养体系中含有不同浓度的一种有丝分裂原以及分别以1.0、2.5或5.0 mM剂量添加的一种酸。通过将氚标记的胸腺嘧啶核苷掺入细胞DNA来测量细胞增殖，并与未添加酸的相同培养物（对照）进行比较。在所有有丝分裂原存在的情况下，均发现随着培养物中丙酸浓度的增加，其具有持续且渐进的抑制作用，并且在商陆有丝分裂原存在时更为明显。在甲基丙二酸存在的情况下，淋巴细胞增殖未发生改变。仅当在培养开始时（植物血凝素激活）或培养至24小时（伴刀豆球蛋白A和商陆有丝分裂原激活）添加药物时，才观察到丙酸盐的作用。通过台盼蓝排斥试验评估，用该药物处理后的淋巴细胞活力与未处理的相同淋巴细胞相比无变化，表明无淋巴细胞毒性活性。总之，在丙酸血症患者组织中蓄积的丙酸会导致“体外”免疫抑制，这可能与这些患者反复感染的特征有关。
