POMC PEPTIDE SYNTHESIS BY NORMAL AND AIDS LEUKOCYTES

获得性免疫缺陷综合征(AIDS)致命缺陷是 失血引起的免疫功能的严重缺陷 辅助性T淋巴细胞和最终的所有免疫活性细胞。 关于下丘脑-垂体-肾上腺的研究还很少。 (HPA)轴在艾滋病和艾滋病相关复合体(ARC)中的作用，但 巨细胞病毒肾上腺炎，偶尔会引起肾上腺 不足，令人惊讶地普遍。此外，还有 ARC中肾上腺皮质18-羟基酶活性进行性丧失 和艾滋病，可能反映了一个独立于ACTH的因素的丧失 这刺激了醛固酮的生物合成。与免疫系统的 第一道防线瘫痪，HPA轴线呈均匀分布 在应对感染的压力方面更加重要。 此外，Je Blalock、EM Smith、WJ Meyer 111和他们的同事 已经提出了一系列数据表明免疫活性 细胞产生前阿片黑素皮质素(POMC)多肽以响应 诱导人类白细胞干扰素(HLFN)的相同药物 阿尔法)，POMC的产生由相同的激素调节 调节垂体前叶POMC多肽的分泌，这些 白细胞来源的POMC多肽可能作用于自分泌或 旁分泌方式调节免疫反应，甚至可以 直接刺激肾上腺皮质类固醇的生物合成 脑下垂体切除的动物。这些发现有可能 对免疫调节的根本重要影响 免疫和内分泌系统的反应和相互作用。 然而，仅有的三个试图复制 布拉洛克、史密斯和迈耶的发现完全没有做到这一点 所以。这一点，缺乏来自其他实验室和 适当的方法严谨性问题引发了对以下问题的保留 这项工作，尽管毫无疑问，一些免疫活性 细胞可以在适当的条件下合成POMC多肽。 我们建议严格审查这些研究的基本结果 调查人员使用独立的、被广泛接受的方法，以及 通过(1)检测、量化和表征来扩展它们 白细胞POMC信使核糖核酸含量的测定 免疫细胞和POMC中的白细胞POMC mRNA和多肽 经各种因素刺激后的介质中的多肽，(3) 确定是否存在一种白细胞衍生的多肽 特异性刺激醛固酮的生物合成，(4)定义 免疫细胞的哪一亚群(S)产生POMC多肽作为反应 对特定刺激，(5)测定白细胞POMC多肽 ARC和艾滋病患者的合成受损，以及(6)评估 白细胞POMC多肽的产生受到损害 艾滋病患者的发热性疾病。如果Blalock et的发现 他们都是正确的，他们将得到最严格的 考试和遗嘱 被扩展到定义免疫系统中可能的根本缺陷 ARC与艾滋病的调节及免疫-内分泌相互作用 病人。

The lethal defect in acquired immune deficiency syndrome (AIDS) is the profound defect in immune function caused by initial loss of helper T lymphocytes and eventually of all immune competent cells. Little has been published about hypothalamic-pituitary-adrenal (HPA) axis function in AIDS and AIDS-related complex (ARC), but cytomegalovirus adrenalitis, occasionally causing adrenal insufficiency, is surprisingly common. In addition, there is progressive loss of adrenocortical 18-hydroxylase activity in ARC and AIDS, perhaps reflecting loss of a factor separate from ACTH that stimulates aldosterone biosynthesis. With the immune system's first line of defense crippled, the HPA axis assumes an even greater importance in responding to the stress of infection. Furthermore, JE Blalock, EM Smith, WJ Meyer 111 and their coworkers have presented a body of data which indicate that immunocompetent cells produce proopiomelanocortin (POMC) peptides in response to the same agents that induce human leukocyte interferon (hlFN alpha), that POMC production is regulated by the same hormones that regulate anterior pituitary POMC peptide secretion and that these leukocyte-derived POMC peptides may act in an autocrine or paracrine fashion to modulate the immune response and can even directly stimulate adrenocortical steroid biosynthesis in hypophysectomized animals. These findings have potentially fundamentally important implications for regulation of the immune response and interaction of the immune and endocrine systems. However, the only three groups that have attempted to reproduce the findings of Blalock, Smith and Meyer have failed completely to do so. This, the lack of supporting data from other laboratories and questions of proper methodologic rigor raise reservations about this work, although there is little doubt that some immunocompetent cells can synthesize POMC peptides under appropriate conditions. We propose to examine rigorously the essential findings of these investigators, using independent, widely-accepted methods, and extend them by (1) detecting, quantifying and characterizing leukocyte POMC mRNA, (2) determining the concentrations of leukocyte POMC mRNA and peptides in the immune cells and POMC peptides in the medium after stimulation by various agents, (3) determining if there is a leukocyte-derived peptide that specifically stimulates aldosterone biosynthesis, (4) defining which subset(s) of immune cells produce POMC peptides in response to specific stimuli, (5) determining if leukocyte POMC peptide synthesis is impaired in ARC and AIDS and (6) assessing whether leukocyte POMC peptide production is impaired in response to febrile illnesses in AIDS patients. If the findings of Blalock et al are correct, they will be confirmed by the most rigorous examination and will be extended to define possible fundamental defects in immune regulation and immune-endocrine interactions in ARC and AIDS patients.