Lorr N A, Golemboski K A, Hemendinger R A, Dietert R R, Bloom S E
Department of Avian and Aquatic Animal Medicine, Cornell University, Ithaca, New York 14853.
Arch Toxicol. 1992;66(8):560-6. doi: 10.1007/BF01973386.
The level of expression of the cytochrome P450 system in an immune tissue could influence the sensitivity of that immune tissue to damage by xenobiotics. The capacity of immune organs and their cellular components for P450I-catalyzed metabolism was assayed in the 4-week-old chicken using the P450I-specific ethoxyresorufin-O-deethylase (EROD) assay and the P450I-inducer, 3,4,3',4'-tetrachlorobiphenyl (TCB). After induction by TCB, EROD was detectable in microsomes from whole thymus, bursa and in peritoneal exudate cells (containing primarily macrophages) at levels of 28.3, 7.2 and 1.3 pmol/mg microsomal protein/min, respectively; the level in control liver was 89.9 pmol/mg microsomal protein/min. No activity was detected in these immune tissues without induction. The P450I specific in vitro inhibitor, alpha-naphthoflavone (NF) inhibited the TCB-induced liver and immune tissue EROD by 50% at concentrations in the range of 0.07-0.1 microM. The cellular distribution of EROD in the bursa and thymus was studied in lymphocytes and supporting tissue cells after their separation by density gradient centrifugation. Much higher TCB-induced EROD was detected in immune tissue supporting cells than in lymphocytes, particularly in the thymus. The P450I in the supporting tissue of the bursa and thymus at 1 week post-hatch was also measured after eradication of the lymphocytes in both immune tissues by in ovo administration of CP. TCB-induced EROD was 12-fold higher in the lymphocyte-depleted thymus than in normal thymus, with a less marked but similar pattern in the bursa.(ABSTRACT TRUNCATED AT 250 WORDS)
细胞色素P450系统在免疫组织中的表达水平可能会影响该免疫组织对外源生物活性物质损伤的敏感性。采用P450I特异性乙氧异吩恶唑酮-O-脱乙基酶(EROD)检测法和P450I诱导剂3,4,3',4'-四氯联苯(TCB),对4周龄鸡的免疫器官及其细胞成分进行P450I催化代谢能力的检测。经TCB诱导后,在整个胸腺、法氏囊的微粒体以及腹腔渗出细胞(主要含巨噬细胞)中均可检测到EROD,其水平分别为28.3、7.2和1.3 pmol/mg微粒体蛋白/分钟;对照肝脏中的水平为89.9 pmol/mg微粒体蛋白/分钟。未诱导时,在这些免疫组织中未检测到活性。P450I特异性体外抑制剂α-萘黄酮(NF)在0.07 - 0.1 microM浓度范围内可使TCB诱导的肝脏和免疫组织EROD活性降低50%。通过密度梯度离心分离淋巴细胞和支持组织细胞后,研究了法氏囊和胸腺中EROD的细胞分布。在免疫组织支持细胞中检测到的TCB诱导的EROD远高于淋巴细胞,尤其是在胸腺中。在孵化后1周,通过在卵内注射环磷酰胺清除两个免疫组织中的淋巴细胞后,还测定了法氏囊和胸腺支持组织中的P450I。淋巴细胞耗竭的胸腺中TCB诱导的EROD比正常胸腺高12倍,法氏囊中也有不太明显但类似的模式。(摘要截短至250字)