Goey H, Keller J R, Back T, Longo D L, Ruscetti F W, Wiltrout R H
Laboratory of Experimental Immunology, NCI-Frederick Cancer Research Facility, MD 21701-1013.
J Immunol. 1989 Aug 1;143(3):877-80.
Transforming growth factor-beta 1 (TGF beta 1) has been shown in vitro to be a potent negative regulator of growth and differentiation of early hemopoietic progenitor cells, but not of more mature progenitors. However, little information is yet available regarding similar effects in vivo. We have developed an approach whereby TGF beta 1 can be administered locoregionally to the bone marrow via direct injection into the femoral artery. Our studies show that intrafemoral administration of a single bolus dose of TGF beta 1 potently inhibits the baseline and IL-3-driven proliferation of bone marrow cells. This inhibition is relatively selective for the earlier multipotential granulocyte, erythroid, megakaryocyte, and macrophage CFU progenitor cells since these are completely inhibited while the more differentiated CFU assayed in culture colonies are inhibited by about 50%. The inhibition of hemopoietic progenitor growth and differentiation is both time and dose dependent with the maximal effect on the marrow observed at 24 h with doses greater than or equal to 5 micrograms/mouse, and the effect is reversed at later times. A possible practical implication of these in vivo results could be the use of TGF beta 1 to protect stem cells in the bone marrow from the myelotoxic effects of chemotherapeutic drugs.
转化生长因子-β1（TGFβ1）在体外已被证明是早期造血祖细胞生长和分化的有效负调节因子，但对更成熟的祖细胞则不然。然而，关于其在体内的类似作用，目前仍知之甚少。我们开发了一种方法，通过直接注入股动脉将TGFβ1局部给予骨髓。我们的研究表明，经股内给予单次推注剂量的TGFβ1可有效抑制骨髓细胞的基础增殖和IL-3驱动的增殖。这种抑制作用对较早的多能粒细胞、红系、巨核细胞和巨噬细胞CFU祖细胞具有相对选择性，因为这些细胞被完全抑制，而在培养集落中检测的更分化的CFU被抑制约50%。造血祖细胞生长和分化的抑制作用具有时间和剂量依赖性，在24小时时，剂量大于或等于5微克/小鼠时对骨髓的影响最大，且在随后的时间作用会逆转。这些体内结果的一个可能实际意义可能是利用TGFβ1保护骨髓中的干细胞免受化疗药物的骨髓毒性作用。
