Stenzel K H, Rubin A L, Novogrodsky A
J Immunol. 1981 Dec;127(6):2469-73.
We report here that hemin, an agent known to induce cellular differentiation in Friend erythroleukemia cells, induces mitogenesis in human T cells and enhances mitogenic responses to supraoptimal concentrations of Con A. Mitogenesis induced by suboptimal or optimal concentrations of Con A is not affected by concentrations of hemin that markedly potentiate responses to supraoptimal amounts of Con A. Maximum mitogenic responses are reached 4 to 5 days after initiation of the cultures. The mitogenic response is macrophage dependent, whereas enhancement of responses to supraoptimal concentrations of Con A is not. Indeed, a greater degree of enhancement is observed after removal of adherent cells. Responses to other mitogens (phytohemagglutinin, wheat germ agglutinin, and sodium periodate) are also enhanced by hemin. Compounds that are metabolically or structurally related to hemin are neither mitogenic nor co-mitogenic. Protoporphyrin IX, which is nonmitogenic, is rendered mitogenic by the chemical insertion of iron to form hemin. Hemin does not affect Con A binding to lymphocytes. These findings indicate that hemin is a macrophage-dependent T cell mitogen with the unusual and remarkable property of overcoming the inhibition of mitogenesis induced by high concentrations of Con A. Since hemin has a limited number of metabolic effects, it provides a useful probe for determination of molecular events associated with lymphocyte activation.
我们在此报告，已知可诱导Friend红白血病细胞发生细胞分化的血红素，可诱导人T细胞发生有丝分裂，并增强对超最佳浓度刀豆蛋白A的有丝分裂反应。亚最佳或最佳浓度刀豆蛋白A诱导的有丝分裂不受血红素浓度的影响，而血红素浓度可显著增强对超最佳量刀豆蛋白A的反应。培养开始后4至5天达到最大有丝分裂反应。有丝分裂反应依赖巨噬细胞，而对超最佳浓度刀豆蛋白A反应的增强则不依赖巨噬细胞。事实上，去除贴壁细胞后观察到更大程度的增强。血红素也增强了对其他有丝分裂原（植物血凝素、麦胚凝集素和高碘酸钠）的反应。与血红素代谢或结构相关的化合物既无促有丝分裂作用也无协同促有丝分裂作用。无促有丝分裂作用的原卟啉IX通过化学插入铁形成血红素后变得具有促有丝分裂作用。血红素不影响刀豆蛋白A与淋巴细胞的结合。这些发现表明，血红素是一种依赖巨噬细胞的T细胞有丝分裂原，具有克服高浓度刀豆蛋白A诱导的有丝分裂抑制这一不同寻常且显著的特性。由于血红素的代谢作用有限，它为确定与淋巴细胞活化相关的分子事件提供了一种有用的探针。
