Production of granulocyte colony-stimulating factor and granulocyte/macrophage-colony-stimulating factor after interleukin-1 stimulation of marrow stromal cell cultures from normal or aplastic anemia donors

✍ Scribed by Anna Rita Migliaccio; Giovanni Migliaccio; John W. Adamson; Beverly Torok-Storb

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 802 KB
• Volume: 152
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041520125

✦ Synopsis

We have studied stromal cell function in naive or interleukin-1 (IL-1)-stimulated (100 pgiml) long-term marrow cultures (LTC) from 1 2 normal donors and 21 patients with severe aplastic anemia (AA). Conditioned media (CM) from normal LTC contained levels of erythroid burst-promoting activity (BPA) and granulocyte/ macrophage (GM) colony-stimulating activity (CSA) comparable to those previously described (Migliaccio et al., 119901 Blood, 75:305-312). The addition of IL-1 to these cultures increased the level of CSA and, specifically, of granulocyte colony-stimulating factor (G-CSF) released. Anti-GM-CSF antibody neutralized BPA and CSA in normal naive LTC C M but only the CSA in the C M from IL-1stimulated LTC. Since the concentrations of GM-CSF, as detected with a specific immunoassay, did not increase after IL-l treatment, these data suggest that IL-Istimulated cultures contain an unidentified growth factor having BPA. C M from AA stromal cells contained levels of CSA comparable to those observed in normal strornal cell C M but had significantly lower levels of BPA. Neither anti-GM-CSF nor anti-IL-3 antibodies neutralized the BPA in AA stromal cell CM. This activity may be related to that found in the C M of IL-1-treated normal stromal cells. In nearly 50% of stromal cell cultures of AA patients, addition of IL-l failed to increase the BPA, CSA, or G-CSF. The presence of an inhibitor in naive or IL-I-treated AA stromal cell C M was excluded by adding the CM to IL-3-stimulated cultures. These findings suggest that G-CSF and GM-CSF genes are differentially regulated in the marrow microenvironment. Furthermore, a marrow microenvironment, deficient in BPA production and, in some cases, unresponsive to IL-1 could contribute to marrow failure in some patients with AA.