Israels L G, Israels S J, Begleiter A, Verburg L, Schwartz L, Mowat M R, Johnston J B
Manitoba Institute of Cell Biology, Manitoba Cancer Treatment and Research Foundation, Winnipeg, Canada.
Leuk Res. 1993 Jan;17(1):81-7. doi: 10.1016/0145-2126(93)90144-a.
TGF-beta is an important immunoregulator as it suppresses proliferation and function of B- and T-lymphocytes. In the present study we have examined the cellular localization and secretion of TGF-beta in B-cells from normal donors and patients with CLL and have assessed the influence of TGF-beta 1 on DNA synthesis in these cells. Using anti-LC(1-30)--a polyclonal anti-TGF-beta 1 antibody--TGF-beta was localized to discrete sites within the cytoplasm of both normal and malignant lymphocytes. These areas co-localized with areas detected by an antigranule antibody (D545), suggesting that TGF-beta may be stored within cytoplasmic secretory vesicles. Both normal B- and CLL cells contained low or undetectable levels of TGF-beta mRNA and secreted low and equivalent amounts of TGF-beta. Compared to untreated cells, DNA synthesis was reduced by TGF-beta 1 to a mean +/- S. E. of 0.84 +/- 0.07 in CLL cells and this was significantly less (p < 0.001) than that observed in normal B-cells (mean +/- S. E. of control, 0.12 +/- 0.02). In 3 of the 18 patients, TGF-beta 1 stimulated DNA synthesis. The reduced inhibition of leukemic cell DNA synthesis by TGF-beta 1 in CLL may provide these cells with a growth or survival advantage over normal lymphocytes and contribute to their selective accumulation.
转化生长因子-β（TGF-β）是一种重要的免疫调节因子，因为它能抑制B淋巴细胞和T淋巴细胞的增殖及功能。在本研究中，我们检测了正常供体和慢性淋巴细胞白血病（CLL）患者B细胞中TGF-β的细胞定位和分泌情况，并评估了TGF-β1对这些细胞DNA合成的影响。使用抗LC(1-30)（一种多克隆抗TGF-β1抗体），TGF-β定位于正常和恶性淋巴细胞胞质内的离散部位。这些区域与抗颗粒抗体（D545）检测到的区域共定位，提示TGF-β可能储存于胞质分泌小泡中。正常B细胞和CLL细胞中TGF-βmRNA水平均较低或无法检测到，且分泌的TGF-β量少且相当。与未处理细胞相比，TGF-β1使CLL细胞的DNA合成降低至平均±标准误为0.84±0.07，这显著低于正常B细胞（对照平均±标准误为0.12±0.02，p<0.001）。在18例患者中有3例，TGF-β1刺激了DNA合成。CLL中TGF-β1对白血病细胞DNA合成的抑制作用降低，可能使这些细胞相对于正常淋巴细胞具有生长或生存优势，并有助于它们的选择性积聚。
