Babiker-Mohamed H, Olsson M L, Boketoft A, Lögdberg L, Akerström B
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
Immunobiology. 1990 Feb;180(2-3):221-34. doi: 10.1016/S0171-2985(11)80330-X.
Human alpha 1-microglobulin (alpha 1-m), a 26 kilodalton serum glycoprotein, was found to exert mitogenic effects on human peripheral blood lymphocytes (PBL) in serum-free medium. Purified T cells, but not B cells, responded with proliferation to alpha 1-m, but only in the presence of monocytes. The mitogenic activity could be partially neutralized by a mouse monoclonal antibody against alpha 1-m. The mitogenicity was species-specific, since alpha 1-m homologues from rats, guinea pigs and rabbits had no effect on human PBL. In a previous study, no effect of alpha 1-m was seen on PBL in the presence of 20% serum, and, therefore, we studied the influence of different concentrations of serum on the alpha 1-m-induced mitogenicity. Thus, human serum enhanced the mitogenic effects of alpha 1-m on human PBL at 1% concentration (v/v) and suppressed the effects at 10%. The suppressing effect of serum at 10%, but not the enhancing effect at 1%, seemed to be conserved among several species. To test the effect of serum proteins of different molecular sizes, human autologous serum was separated by gel chromatography on Sephadex G-200 into four fractions. Fractions 1 and 2 (roughly containing proteins larger than 100 kilodaltons) suppressed the mitogenic effects of alpha 1-m, while fractions 3 and 4 enhanced the stimulation by alpha 1-m, at 0.5% and concentrations above. It is concluded that the mitogenic effect of alpha 1-m on lymphocytes is regulated by several serum factors, both enhancing and suppressive, that does not have any proliferative effect of their own. It can be speculated that the balance between enhancing and suppressing co-factors in the blood determines the degree of the stimulation of lymphocytes by alpha 1-m. This is compatible with an immunomodulatory role for alpha 1-m, in spite of its relatively constant plasma levels in health and disease.
人α1-微球蛋白(α1-m)是一种一种一种一种26千道尔顿的血清糖蛋白,发现在无血清培养基中对人外周血淋巴细胞(PBL)具有促有丝分裂作用。纯化的T细胞而非B细胞对α1-m有增殖反应,但仅在单核细胞存在时。抗α1-m的小鼠单克隆抗体可部分中和其促有丝分裂活性。这种促有丝分裂活性具有物种特异性,因为来自大鼠、豚鼠和兔子的α1-m同源物对人PBL没有影响。在先前的一项研究中,在20%血清存在的情况下未观察到α1-m对PBL有影响,因此,我们研究了不同浓度血清对α1-m诱导的促有丝分裂作用的影响。结果发现,人血清在1%(v/v)浓度时增强了α1-m对人PBL的促有丝分裂作用,而在10%浓度时则抑制了该作用。血清在10%时的抑制作用而非1%时的增强作用似乎在几个物种中是保守的。为了测试不同分子大小的血清蛋白的作用,人自体血清通过Sephadex G-200凝胶色谱法分离为四个组分。组分1和2(大致包含大于100千道尔顿的蛋白质)抑制了α1-m的促有丝分裂作用,而组分3和4在0.5%及以上浓度时增强了α1-m的刺激作用。得出的结论是,α1-m对淋巴细胞的促有丝分裂作用受几种血清因子调节,既有增强作用也有抑制作用,而这些因子自身没有任何增殖作用。可以推测,血液中增强和抑制辅助因子之间的平衡决定了α1-m对淋巴细胞的刺激程度。这与α1-m的免疫调节作用是相符的,尽管其在健康和疾病状态下血浆水平相对恒定。