Sugimoto K, Taniguchi S, Ogata H, Ikehara S, Fujita J, Mori K J
Department of Physiology and Biochemistry, Faculty of Science, Niigata University, Japan.
Leuk Res. 1992 Sep;16(9):889-97. doi: 10.1016/0145-2126(92)90035-6.
When spleen cells of mice grafted with STIL-3 C5 cells, a leukemic T-cell line producing IL-3, are cultured in vitro, a high IL-3 activity is detectable in the culture supernatant. However, when bone marrow cells of the same grafted mice are cultured under similar conditions, hardly any IL-3 activity is detectable. To elucidate the mechanism of this difference, we examined whether the bone marrow cells either suppress IL-3 production by STIL-3 C5 cells or produce an IL-3 inhibitor. When STIL-3 C5 cells were cultured in the presence of normal bone marrow cells, the culture supernatant showed a significantly reduced IL-3 activity as assessed by growth stimulatory effects on IL-3-dependent DA-1 cells and mast cells. The conditioned medium (CM) did not inhibit the growth of IL-3-independent cell lines. Heat treatment of the CM resulted in a recovery of the IL-3 activity, indicating that the effect was mediated by a heat-labile inhibitor rather than by suppression of IL-3 production. CM of bone marrow cells alone did not inhibit the IL-3 activity. The inhibitor was produced by a stem cell-enriched fraction of the bone marrow, and not by fractions of T cells, granulocytes, or adherent cells including macrophages. Stimulation of the stem cell-enriched fraction of bone marrow with STIL-3 C5-CM also induced the production of the IL-3 inhibitor, which was recovered in a MW 50-100 kD fraction after ultrafiltration. These results suggest a possible presence of a feedback mechanism against the IL-3 effect on hemopoietic stem cells and progenitors in the bone marrow.
当用产生白细胞介素-3（IL-3）的白血病T细胞系STIL-3 C5细胞移植的小鼠脾细胞在体外培养时，在培养上清液中可检测到高IL-3活性。然而，当相同移植小鼠的骨髓细胞在类似条件下培养时，几乎检测不到任何IL-3活性。为了阐明这种差异的机制，我们研究了骨髓细胞是否抑制STIL-3 C5细胞产生IL-3或产生IL-3抑制剂。当STIL-3 C5细胞在正常骨髓细胞存在下培养时，通过对IL-3依赖的DA-1细胞和肥大细胞的生长刺激作用评估，培养上清液显示IL-3活性显著降低。条件培养基（CM）不抑制IL-3非依赖细胞系的生长。对CM进行热处理导致IL-3活性恢复，表明该效应是由一种热不稳定抑制剂介导的，而不是通过抑制IL-3产生。单独的骨髓细胞CM不抑制IL-3活性。该抑制剂由骨髓中富含干细胞的部分产生，而不是由T细胞、粒细胞或包括巨噬细胞在内的贴壁细胞部分产生。用STIL-3 C5-CM刺激骨髓中富含干细胞的部分也诱导了IL-3抑制剂的产生，超滤后在分子量50-100 kD的部分中回收。这些结果表明骨髓中可能存在针对IL-3对造血干细胞和祖细胞作用的反馈机制。
