Weiser W Y, Pozzi L M, David J R
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1991 Sep 15;147(6):2006-11.
A recombinant form of the first lymphokine to be discovered, migration inhibitory factor (rMIF) was obtained from COS-1 cells transfected with a cDNA library from a human T cell hybridoma (6). rMIF has an amino acid sequence unrelated to that of any known protein. To learn more about the biology of MIF, we tested its ability to effect the survival of Leishmania donovani in macrophages. We found that rMIF activates blood monocyte-derived macrophages in vitro to suppress the growth of and kill these intracellular parasites. The anti-leishmanial effect (ranging from 50 to 77% reduction of parasites) is maximal when macrophages have been incubated with rMIF 48 to 72 h before infection and is similar to that seen with macrophages activated by IFN-gamma. Of interest, whereas the activation of human macrophages by IFN-gamma is inhibited by IL-4 and not enhanced by LPS, the activation by rMIF is enhanced by LPS but is not inhibited by IL-4. The data presented here demonstrate that rMIF is a potent activator of macrophages and is likely to be critical in cell-mediated immune host defenses.
迁移抑制因子(rMIF)是首个被发现的淋巴因子的重组形式,它是从用人类T细胞杂交瘤的cDNA文库转染的COS-1细胞中获得的(6)。rMIF的氨基酸序列与任何已知蛋白质的序列均不相关。为了更多地了解MIF的生物学特性,我们测试了其影响杜氏利什曼原虫在巨噬细胞中存活的能力。我们发现,rMIF在体外可激活血液单核细胞衍生的巨噬细胞,以抑制并杀死这些细胞内寄生虫。当巨噬细胞在感染前48至72小时与rMIF孵育时,抗利什曼原虫作用(寄生虫减少50%至77%)最大,且与经γ干扰素激活的巨噬细胞所观察到的作用相似。有趣的是,γ干扰素对人类巨噬细胞的激活作用会被白细胞介素-4抑制,且不会因脂多糖而增强,而rMIF的激活作用会因脂多糖而增强,但不会被白细胞介素-4抑制。此处呈现的数据表明,rMIF是巨噬细胞的强效激活剂,可能在细胞介导的免疫宿主防御中起关键作用。