Stanović S, Boranić M, Petrovecki M, Nemet D, Skodlar J, Golubić-Cepulić B, Batinić D, Labar B
Ruder Boskovic Institute, Department of Molecular Medicine, Zagreb, Croatia.
Biomed Pharmacother. 1998;52(9):397-402. doi: 10.1016/S0753-3322(99)80008-0.
Thiorphan, a specific inhibitor of membrane neutral endopeptidase (NEP, EC 3.4.24.11) also known as the common acute lymphoblastic leukemia antigen (CALLA, CD10) was added into short-term clonal cultures of the buffy coat concentrates of human bone marrow obtained from a healthy donor (six experiments) and from ten patients with non-Hodgkin lymphoma (NHL) (eight in complete remission, one in partial remission and one in relapse). Thiorphan concentrations ranged from 10(-5) to 10(-13) M. Nanomolar and higher concentrations of the drug mildly stimulated the granulocyte-macrophage colony-forming unit (GM-CFU) counts in the cultures of normal bone marrow, reaching the significance at 10(-7) M. Meaningful alterations of the GM-CFU counts were noted in 31 of 79 thiorphan-treated cultures of NHL bone marrow (39%). In those cultures the stimulatory effects (33%) outnumbered the inhibitory ones (6%). The stimulatory effects occurred mainly in the bone marrow samples of the patients with highly malignant NHL. The observations are compatible with the idea that the membrane endopeptidase (CALLA, CD10) participates in processes controlling the proliferation and differentiation of hematopoetic cells by cleaving the neuropeptides and related hemoregulatory peptides.
硫磷酰胺，一种膜中性内肽酶（NEP，EC 3.4.24.11）的特异性抑制剂，也被称为普通急性淋巴细胞白血病抗原（CALLA，CD10），被添加到从一名健康供体获取的人骨髓血沉棕黄层浓缩物的短期克隆培养物中（六个实验），以及从十名非霍奇金淋巴瘤（NHL）患者获取的培养物中（八名完全缓解、一名部分缓解和一名复发）。硫磷酰胺的浓度范围为10^(-5)至10^(-13) M。纳摩尔及更高浓度的该药物轻度刺激正常骨髓培养物中的粒细胞 - 巨噬细胞集落形成单位（GM - CFU）计数，在10^(-7) M时达到显著水平。在79个经硫磷酰胺处理的NHL骨髓培养物中有31个（39%）观察到GM - CFU计数有显著变化。在这些培养物中，刺激作用（33%）超过抑制作用（6%）。刺激作用主要发生在高恶性NHL患者的骨髓样本中。这些观察结果与膜内肽酶（CALLA，CD10）通过裂解神经肽和相关血液调节肽参与控制造血细胞增殖和分化过程的观点相符。
