Sandler J A, Smith T K, Manganiello V C, Kirkpatrick C H
J Clin Invest. 1975 Nov;56(5):1271-9. doi: 10.1172/JCI108203.
We studied the effects of dialysates from leukocyte lysates containing dialyzable transfer factor activity and other leukocyte dialysates devoid of transfer factor activity on accumulation of cyclic nucleotides in human leukocytes. Dialysates from normal leukocytes produced 4- to 11-fold increases in leukocyte cGMP, and experiments with purified cell populations revealed that the increases were predominantly, if not entirely, in blood monocytes. Substances that increased monocyte cGMP could be obtained from several cell populations including mononuclear cells from Hypaque-Ficoll gradients, plastic-adherent monocytes, nonadherent lymphocytes, and neutrophils, but were not present in dialysates of leukemic lymphocytes from patients with the Sezary syndrome. Moreover, dialysates that increased leukocyte cGMP had essentially no effect on intracellular cAMP. Dialysates of lysed mononuclear cells contained serotonin, ascorbate, and an unidentified cholinergic activity, agents known to increase leukocyte cGMP. After passage of dialyzable transfer factor from mononuclear cells through a gel-filtration column, four fractions were obtained that increased leukocyte cGMP. Two of these fractions contained ascorbate; two other active fractions, including one that also caused conversion of delayed skin tests, did not contain detectable ascorbate or serotonin. The dialysate of lysed neutrophils also increased cGMP, but this activity was limited to the column fractions which contained ascorbic acid. These observations raise the possibility that alterations in monocyte cGMP content could modulate either the specific antigen-dependent, or, more likely, the antigen-independent activities in preparations of transfer factor.
我们研究了含有可透析转移因子活性的白细胞裂解物透析液以及其他缺乏转移因子活性的白细胞透析液对人白细胞中环核苷酸积累的影响。正常白细胞透析液可使白细胞cGMP增加4至11倍，对纯化细胞群体的实验表明，这种增加主要（如果不是完全）发生在血液单核细胞中。能增加单核细胞cGMP的物质可从多个细胞群体中获得，包括来自Hypaque-Ficoll梯度的单核细胞、塑料贴壁单核细胞、非贴壁淋巴细胞和中性粒细胞，但在Sezary综合征患者的白血病淋巴细胞透析液中不存在。此外，增加白细胞cGMP的透析液对细胞内cAMP基本没有影响。裂解单核细胞的透析液含有血清素、抗坏血酸盐和一种未鉴定的胆碱能活性物质，这些物质已知可增加白细胞cGMP。单核细胞的可透析转移因子通过凝胶过滤柱后，得到了四个能增加白细胞cGMP的组分。其中两个组分含有抗坏血酸盐；另外两个活性组分，包括一个也能引起迟发型皮肤试验转化的组分，不含可检测到的抗坏血酸盐或血清素。裂解中性粒细胞的透析液也能增加cGMP，但这种活性仅限于含有抗坏血酸的柱组分。这些观察结果提示，单核细胞cGMP含量的改变可能调节转移因子制剂中特异性抗原依赖性或更可能是抗原非依赖性的活性。
