Buzzetti R, Ciancio A, Ciucci E, Celli V, Giovannini C
Cattedra di Neuroendocrinologia, Università degli Studi di Roma La Sapienza.
Ann Ital Med Int. 1991 Oct-Dec;6(4):357-63.
Evidence has accumulated that human peripheral blood mononuclear cells (PBMC) may release adrenocorticotropic hormone (ACTH) and endorphin-like peptides into the culture medium when stimulated with different substances such as Newcastle disease virus and the lipopolysaccharide of Escherichia coli. However, to our knowledge, no quantitative assessment of ACTH-LIR (like-immunoreactivity) in human PBMC has been reported. We thus utilized a radioimmunoassay for ACTH to find a median of 30 pg of ACTH-LIR in 10(7) PBMC of 11 normal subjects. ACTH-LIR was also detected in 7 different cell lines derived from patients with lymphoid and myeloid malignancies, two of them, JM and U937, showed values of 135 and 108 pg/10(7) cells respectively. Stimulation with IL-1 beta at the concentration of 1000 U/mL induced, after 48 h, a significant increase of intralymphocytic ACTH levels when compared to basal and 24 h values. The chromatographic characterization of this ACTH-LIR showed, at least, three molecular forms of immunoreactive ACTH; molecular weights were 31 kD POMC, 22 kD ACTH and 4.5 kD ACTH. We used northern blotting with human genomic DNA probe for POMC gene to evidence specific mRNA in PBMC; mRNA was also observed in a T lymphocyte cell line derived from a patient with lymphoma. We conclude that PBMC produce ACTH-LIR which may act as a paracrine immunomodulator similar to lymphokine and/or may signal the adrenal gland to secrete glucocorticoids.
有证据表明,当受到新城疫病毒和大肠杆菌脂多糖等不同物质刺激时,人类外周血单核细胞(PBMC)可能会将促肾上腺皮质激素(ACTH)和内啡肽样肽释放到培养基中。然而,据我们所知,尚未有关于人类PBMC中ACTH-LIR(类免疫反应性)的定量评估报告。因此,我们利用ACTH放射免疫分析法在11名正常受试者的10⁷个PBMC中发现ACTH-LIR的中位数为30 pg。在源自淋巴和髓系恶性肿瘤患者的7种不同细胞系中也检测到了ACTH-LIR,其中两种细胞系JM和U937,其ACTH-LIR值分别为135和108 pg/10⁷个细胞。与基础值和24小时的值相比,在48小时后,1000 U/mL浓度的IL-1β刺激可诱导淋巴细胞内ACTH水平显著升高。对这种ACTH-LIR的色谱分析显示,至少有三种免疫反应性ACTH的分子形式;分子量分别为31 kD POMC、22 kD ACTH和4.5 kD ACTH。我们使用人类基因组DNA探针进行Northern印迹分析以检测PBMC中POMC基因的特异性mRNA;在源自一名淋巴瘤患者的T淋巴细胞系中也观察到了mRNA。我们得出结论,PBMC产生ACTH-LIR,其可能作为一种旁分泌免疫调节剂,类似于淋巴因子,和/或可能向肾上腺发出信号以分泌糖皮质激素。