Smith E M, Hughes T K, Hashemi F, Stefano G B
Department of Psychiatry, University of Texas Medical Branch, Galveston 77550.
Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):782-6. doi: 10.1073/pnas.89.2.782.
The activation of human granulocytes and invertebrate immunocytes was found to be suppressed by corticotropin (ACTH) and melanotropin (MSH). In spontaneously active granulocytes both neuropeptides caused significant conformational changes indicative of inactivity plus a reduction in their locomotion. Significant inactivation of human granulocytes by ACTH required 2 hr, that by MSH only 20 min. The addition to the incubation medium of phosphoramidon, a specific inhibitor of neutral endopeptidase 24.11, blocked inactivation of granulocytes by ACTH. Radioimmunoassay for MSH of supernatant fluids from granulocytes incubated with ACTH demonstrated a time-dependent increase in MSH. These data strongly indicate that the effect of ACTH is largely due to its conversion to MSH by granulocyte-associated neutral endopeptidase. Parallel experiments with immunocytes from the mollusc Mytilus edulis gave similar results, indicating the universality of this phenomenon. Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections.
已发现促肾上腺皮质激素（ACTH）和促黑素（MSH）可抑制人类粒细胞和无脊椎动物免疫细胞的激活。在自发活跃的粒细胞中，这两种神经肽都会引起显著的构象变化，表明其活性降低，同时其运动能力也会下降。ACTH使人类粒细胞显著失活需要2小时，而MSH仅需20分钟。向孵育培养基中添加中性内肽酶24.11的特异性抑制剂磷酰胺素，可阻断ACTH对粒细胞的失活作用。对与ACTH一起孵育的粒细胞上清液进行MSH放射免疫测定，结果显示MSH呈时间依赖性增加。这些数据有力地表明，ACTH的作用很大程度上是由于它被粒细胞相关的中性内肽酶转化为MSH。用贻贝的免疫细胞进行的平行实验也得到了类似结果，表明这一现象具有普遍性。我们发现，在几种病毒中，人类免疫缺陷病毒可诱导H9 T淋巴瘤细胞产生ACTH和MSH，这表明这些神经肽在这类感染所特有的免疫抑制中起重要作用。
