Induction of leukemia cell differentiation and apoptosis by recombinant P48, a modulin derived from Mycoplasma fermentans.
Induction of leukemia cell differentiation and apoptosis by recombinant P48, a modulin derived from Mycoplasma fermentans.
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DOI：
10.1006/bbrc.2000.2282
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发表时间：
2000-03
影响因子：
3.1
通讯作者：
R. Hall;S. Agarwal;D. Kestler
中科院分区：
文献类型：
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作者：
R. Hall;S. Agarwal;D. Kestler
P48 是一种 48 kDa 单核细胞分化/激活因子，最初在 Reh 和其他白血病细胞系的条件培养基中发现，最近被证明是发酵支原体基因产物。此前，条件培养基 P48 已被证明可诱导 HL-60（人早幼粒细胞白血病）细胞的分化。最近，我们实验室从Reh细胞中分离出P48的cDNA克隆，从发酵支原体中分离出P48的基因组克隆，并在大肠杆菌中将重组蛋白表达为麦芽糖结合蛋白（MBP）融合蛋白。在本报告中，我们介绍了这种重组 P48 融合蛋白 (rP48-MBP) 的初步表征。我们发现 rP48-MBP 诱导 HL-60、U937（人组织细胞淋巴瘤）和 M1（小鼠骨髓性白血病）细胞系的分化。有趣的是，通过末端转移酶 (TUNEL) 测定评估，rP48-MBP 还诱导 U937 和 HL-60 细胞凋亡。这是支原体基因产物诱导细胞凋亡的第一份报告。 P48 是一种支原体衍生的免疫调节分子，具有分化和细胞凋亡诱导活性，可能在支原体感染的病理生理学中发挥重要作用。该重组蛋白可用于研究恶性和非恶性造血细胞的分化、细胞因子产生和凋亡的机制。
P48 is a 48-kDa monocytic differentiation/activation factor which was originally identified in the conditioned medium of the Reh and other leukemia cell lines and has recently been shown to be a Mycoplasma fermentans gene product. Previously, conditioned medium P48 has been shown to induce differentiation of HL-60 (human promyelocytic leukemia) cells. Recently our laboratory isolated cDNA clones for P48 from Reh cells and genomic clones from Mycoplasma fermentans and expressed the recombinant protein as a maltose binding protein (MBP) fusion protein in E. coli. In this report we present the initial characterization of this recombinant P48 fusion protein (rP48-MBP). We show that rP48-MBP induces differentiation of HL-60, U937 (human histiocytic lymphoma), and M1 (mouse myeloid leukemia) cell lines. Interestingly, rP48-MBP also induces apoptosis of U937 and HL-60 cells as assessed by terminal transferase (TUNEL) assays. This is the first report of induction of apoptosis by a Mycoplasma gene product. P48 is a Mycoplasma-derived immunomodulatory molecule which has differentiation and apoptosis-inducing activities and may be important in the pathophysiology of Mycoplasma infections. The recombinant protein may be useful in studying the mechanisms of differentiation, cytokine production, and apoptosis in malignant and nonmalignant hematopoietic cells.