Roodman G D, Bird A, Hutzler D, Montgomery W
Audie Murphy VA Hospital, Research Service, San Antonio, TX 78284.
Exp Hematol. 1987 Oct;15(9):928-35.
Macrophages can modulate the growth of hematopoietic progenitors. We have examined the effects of tumor necrosis factor-alpha, a product of activated macrophages, on human erythroid progenitors (CFU-E, BFU-E) and the hematopoietic cell lines K562, HL60, and HEL cells. Tumor necrosis factor (TNF) significantly inhibited CFU-E and BFU-E growth at concentrations as low as 10(-11)-10(-12) M (0.2 U/ml), although erythroid colony and burst formation were not totally ablated. Preincubation of marrow samples with TNF for 15 min was sufficient to suppress erythroid colony and burst formation. Addition of TNF after the start of culture inhibited CFU-E- and BFU-E-derived colony formation if TNF was added within the first 48 h of culture. Additionally, TNF inhibited the growth of highly purified erythroid progenitors harvested from day 5 BFU-E. The colonies which formed in cultures treated with TNF were significantly smaller than those formed in control cultures. TNF (10(-8)-10(-10) M) also suppressed the growth of the hematopoietic cell lines K562, HL60, and HEL cells, with 40%-60% of the cells being sensitive to TNF. Preincubation of HL60 cells with TNF for 15 min significantly inhibited their growth. K562, HL60, and HEL cells expressed high-affinity receptors for TNF in low numbers (6000-10,000 receptors per cell). Fluorescence-activated cell sorter analysis of TNF binding to HEL cells demonstrated that the majority of these cells expressed TNF receptors. These data suggest that: (1) TNF is a rapid irreversible and extremely potent inhibitor of CFU-E, BFU-E, and hematopoietic cell lines K562, HL60, and HEL cells; (2) TNF appears to be acting on a subpopulation of erythroid cells, predominantly CFU-E, BFU-E, and possibly proerythroblasts; (3) TNF appears not to require accessory cells such as lymphocytes or macrophages to inhibit erythroid progenitors; and (4) the presence of TNF receptors on hematopoietic cells is not sufficient to confer sensitivity to TNF since the majority (80%-95%) of HEL cells express TNF receptors while only 40%-60% are inhibited by TNF.
巨噬细胞可调节造血祖细胞的生长。我们研究了活化巨噬细胞的产物肿瘤坏死因子-α对人红系祖细胞（CFU-E、BFU-E）以及造血细胞系K562、HL60和HEL细胞的影响。肿瘤坏死因子（TNF）在低至10^(-11)-10^(-12) M（0.2 U/ml）的浓度下就能显著抑制CFU-E和BFU-E的生长，尽管红系集落和爆式集落形成并未完全被消除。将骨髓样本与TNF预孵育15分钟就足以抑制红系集落和爆式集落的形成。如果在培养的前48小时内添加TNF，那么在培养开始后添加TNF会抑制CFU-E和BFU-E来源的集落形成。此外，TNF抑制了从第5天的BFU-E收获的高度纯化的红系祖细胞的生长。在用TNF处理的培养物中形成的集落明显小于在对照培养物中形成的集落。TNF（10^(-8)-10^(-10) M）也抑制造血细胞系K562、HL60和HEL细胞的生长，其中40%-60%的细胞对TNF敏感。将HL60细胞与TNF预孵育15分钟可显著抑制其生长。K562、HL60和HEL细胞表达少量高亲和力的TNF受体（每个细胞6000-10000个受体）。对TNF与HEL细胞结合的荧光激活细胞分选分析表明，这些细胞中的大多数表达TNF受体。这些数据表明：（1）TNF是CFU-E、BFU-E以及造血细胞系K562、HL60和HEL细胞的快速、不可逆且极其有效的抑制剂；（2）TNF似乎作用于红系细胞的一个亚群，主要是CFU-E、BFU-E，可能还有早幼红细胞；（3）TNF似乎不需要诸如淋巴细胞或巨噬细胞等辅助细胞来抑制红系祖细胞；（4）造血细胞上存在TNF受体不足以赋予对TNF的敏感性，因为大多数（80%-95%）的HEL细胞表达TNF受体，而只有40%-60%被TNF抑制。
