Zhang Shimin, Tsai Shien, Wu Timothy T, Li Bingjie, Shih James W-K, Lo Shyh-Ching
Department of Infectious and Parasitic Diseases Pathology, American Registry of Pathology, Washington DC, USA.
Blood. 2004 Dec 15;104(13):4252-9. doi: 10.1182/blood-2004-04-1245. Epub 2004 Aug 26.
Chronic infection or colonization by mycoplasma(s) could gradually and significantly alter many biologic properties of mammalian host cells in culture, including induction of malignant transformation. We examined effects of Mycoplasma fermentans infection on the continuing survival and immortality of human peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Without specific supplemental growth factors, human PBMCs normally die rapidly, with few cells other than macrophages/monocytes surviving after 2 weeks in cultures. Only occasional Epstein-Barr virus (EBV)-positive B lymphocytes would continue to proliferate and undergo spontaneous immortalization. Our present study revealed that infection of human PBMCs in culture with the incognitus and PG18 strains of M fermentans, but surprisingly not with some other strains tested in parallel, markedly enhanced the rate of EBV-positive B lymphocytes to undergo immortalization (74% vs 17%). Compared with spontaneously immortalized PBMCs, the PBMCs immortalized in cultures infected with the mycoplasmas often had prominent karyotype changes with chromosomal loss, gain, or translocations. Furthermore, many of these immortalized B lymphocytes were found to be monoclonal in nature. The in vitro findings would be of relevance to lymphoproliferative disorders that occurred in patients with immune suppression. The mycoplasma-mediated promotional effect in cell immortalization and its potential clinical implications warrant further study.
支原体的慢性感染或定植可逐渐并显著改变培养的哺乳动物宿主细胞的许多生物学特性,包括诱导恶性转化。我们研究了发酵支原体感染对健康献血者的人外周血单个核细胞(PBMC)持续存活和永生化的影响。在没有特定补充生长因子的情况下,人PBMC通常会迅速死亡,培养2周后除巨噬细胞/单核细胞外几乎没有细胞存活。只有偶尔的爱泼斯坦-巴尔病毒(EBV)阳性B淋巴细胞会继续增殖并发生自发永生化。我们目前的研究表明,用发酵支原体的未知菌株和PG18菌株感染培养中的人PBMC,但令人惊讶的是,用其他一些平行测试的菌株感染则不会,这显著提高了EBV阳性B淋巴细胞永生化的速率(74%对17%)。与自发永生化的PBMC相比,在感染支原体的培养物中永生化的PBMC通常有明显的核型变化,包括染色体丢失、增加或易位。此外,发现许多这些永生化的B淋巴细胞本质上是单克隆的。这些体外研究结果与免疫抑制患者发生的淋巴增殖性疾病有关。支原体介导的细胞永生化促进作用及其潜在的临床意义值得进一步研究。