Barrett A J, Longhurst P, Rosengurt N, Hobbs J R, Humble J G
J Clin Pathol. 1978 Feb;31(2):129-35. doi: 10.1136/jcp.31.2.129.
Clinical preparations of horse antilymphocyteglobulin (ALG) were found to inhibit human bone marrow granulocyte colony growth. This effect was enhanced by complement and was dose dependent, being almost complete at ALG concentrations of 100 microgram/ml. Inhibition was a property of ALG but not of normal horse globulin. However, short incubation of ALG with bone marrow cells occasionally stimulated colony growth and normal horse globulin regularly stimulated it. Three hours' incubation of bone marrow cells with ALG was needed to produce consistent colony inhibition, which was measurable as a reduction in the expected number of colonies and as a fall in the colony: cluster ratio of surviving cell aggregates. Absorption of ALG on acute myeloid leukaemia blast cells removed the inhibiting property of the ALG while preserving its lymphocytotoxic action. Serum from two patients receiving ALG treatment inhibited colony growth for up to 48 hours after ALG administration. The results suggest the presence in ALG of antibodies specifically cytotoxic to myeloid stem cells which may relate to its myleosuppressive properties in vivo, and also indicate that it should be possible to remove antimyeloid antibodies from ALG by absorption. The use of such purified ALG would have advantages in clinical bone marrow transplantation.
已发现马抗淋巴细胞球蛋白(ALG)的临床制剂可抑制人骨髓粒细胞集落生长。补体可增强这种作用,且呈剂量依赖性,在ALG浓度为100微克/毫升时几乎完全抑制。抑制作用是ALG的特性,而非正常马球蛋白的特性。然而,ALG与骨髓细胞短时间孵育偶尔会刺激集落生长,而正常马球蛋白则经常会刺激集落生长。骨髓细胞与ALG孵育3小时才能产生一致的集落抑制,这可通过预期集落数量的减少以及存活细胞聚集体的集落:簇比例的下降来衡量。ALG在急性髓性白血病原始细胞上的吸附消除了ALG的抑制特性,同时保留了其淋巴细胞毒性作用。两名接受ALG治疗患者的血清在给予ALG后长达48小时内抑制集落生长。结果表明ALG中存在对髓样干细胞具有特异性细胞毒性的抗体,这可能与其在体内的骨髓抑制特性有关,并且还表明通过吸附从ALG中去除抗髓样抗体应该是可行的。使用这种纯化的ALG在临床骨髓移植中会具有优势。