Van Vlasselaer P, Falla N, Van Den Heuvel R, Dasch J, de Waal Malefijt R
Department of Environment, Vlaamse Instelling voor Technologisch Onderzoek (VITO), Mol, Belgium.
Clin Orthop Relat Res. 1995 Apr(313):103-14.
Bone marrow from 5-fluorouracil-treated mice support osteogenesis when cultured in the presence of beta-glycerophosphate and vitamin C. These cultures are unable to support the growth of granulocyte/macrophage colony-forming units for longer than 2 weeks. In contrast, granulocyte/macrophage colony-forming units were detected for more than 6 weeks in interleukin-10 (IL-10)-treated cultures. In addition, IL-10-treated cultures contain long-term culture initiating cells, suggesting the presence of pluripotent hematopoietic cells. Apparently, IL-10 does not directly stimulate the proliferation of granulocyte/macrophage colony-forming units. Interleukin-10 is unable to stimulate [3H]-thymidine incorporation or to increase the number of granulocyte/macrophage colony-forming units in cell suspensions harvested from untreated or interleukin-10-treated bone marrow cultures. Interleukin-10 acts via an indirect pathway. Because exogenous transforming growth factor-beta (TGF-beta) reverses IL-10's stimulatory activity on myeloid progenitors, IL-10 most likely works by blocking TGF-beta synthesis, which acts as an endogenous suppressor of hematopoiesis in osteogenic marrow cultures. This is shown further by the increased numbers of granulocyte/macrophage colony-forming units in cultures treated with neutralizing anti TGF-beta antibodies (1D11.16). Interleukin-10 and 1D11.16 change the cultured bone marrow stroma from an osteogenic into a hematopoietic morphology. It may be that by blocking endogenous TGF-beta production, IL-10 drives marrow mesenchymal cells away from osteogenic differentiation toward hematopoietic support.
来自5-氟尿嘧啶处理小鼠的骨髓在β-甘油磷酸酯和维生素C存在的情况下培养时支持成骨作用。这些培养物在超过2周的时间内无法支持粒细胞/巨噬细胞集落形成单位的生长。相比之下，在白细胞介素-10（IL-10）处理的培养物中，粒细胞/巨噬细胞集落形成单位在超过6周的时间内都能被检测到。此外，IL-10处理的培养物含有长期培养起始细胞，这表明存在多能造血细胞。显然，IL-10不会直接刺激粒细胞/巨噬细胞集落形成单位的增殖。白细胞介素-10无法刺激从未经处理或经白细胞介素-10处理的骨髓培养物中收获的细胞悬液中的[3H]-胸腺嘧啶核苷掺入，也无法增加粒细胞/巨噬细胞集落形成单位的数量。白细胞介素-10通过间接途径起作用。因为外源性转化生长因子-β（TGF-β）会逆转IL-10对髓系祖细胞的刺激活性，所以IL-10很可能是通过阻断TGF-β的合成来发挥作用的，TGF-β在成骨骨髓培养物中作为造血的内源性抑制剂。用中和抗TGF-β抗体（1D11.16）处理的培养物中粒细胞/巨噬细胞集落形成单位数量增加，进一步证明了这一点。白细胞介素-10和1D11.16将培养的骨髓基质从成骨形态转变为造血形态。可能是通过阻断内源性TGF-β的产生，IL-10促使骨髓间充质细胞从成骨分化转向造血支持。
