Regulation of early human hematopoietic (BFU-E and CFU-GEMM) progenitor cells in vitro by interleukin 1-induced fibroblast-conditioned medium

Abstract

Stimulators of human erythroid burst-forming units (BFU-E) and multipotential colony-forming cells (CFU-GEMM) can be produced by a number of different cell types. A product of human peripheral blood monocytes, interleukin 1 (IL-1), was evaluated for its ability to stimulate fibroblast cultures to produce stimulators of human bone marrow BFU-E and CFU-GEMM colony formation. BFU-E and CFU-GEMM colony formation was evaluated using low-density, nonadherent low-density, and T lymphocyte-depleted nonadherent low-density human bone marrow cells cultured in the presence of a source of pure human erythropoietin. Both human monocyte conditioned medium (MCM) and human recombinant IL-1 (hrIL-1) induced fibroblasts to produce stimulators of BFU-E and CFU- GEMM in a dose-dependent fashion with maximal colony formation occurring when fibroblasts were stimulated by 25% MCM or 140 ng/mL ROO6B hrIL-1, or 1.25 to 5 ng/mL ROO6T hrIL-1. Preincubation of MCM and hrIL-1 with an antibody to IL-1 inactivated the ability of MCM and hrIL- 1 to induce the release of erythroid and multipotential colony stimulating activity from fibroblasts. These results suggest that monocyte-derived IL-1 is involved in regulating the production of humoral stimulators of early human hematopoietic progenitors.

Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor.

“…Given that we have used a non-specific inflammatory stimulant (LPS) to induce LCM and that both normal and athymic nude animals produce LCM with similar modulating activity, it appears likely that the GM-CSF is of mesenchymal or macrophagic origin, and as such is produced at an early stage of the host response after the initial inflammatory stimulus is encountered. GM-CSF has been shown to be secreted by both airway epithelial cells (23) and macrophages (24) via the direct stimulatory effects of LPS, and in addition, endothelial cells (25), fibroblasts (26), and airway epithelial cells (27) respond to cytokines released by LPS-stimulated macrophages (notably IL-1 and/or TNF-ot) via GM-CSF secretion. All of these cell types are abundant in lung tissue, and thus potentially contribute to local immunoregulation through this pathway.…”

Interleukin 1 enhances growth factor-dependent proliferation of the clonogenic cells in acute myeloblastic leukemia and of normal human primitive hemopoietic precursors.

“…IL-1, long recognized as an important immune mediator, has also proved to be capable of affecting hemopoietic progenitor cell proliferation through at least two different mechanisms . First, IL-1 has been shown by many investigators to indirectly support hemopoietic colony formation by activating different cell types to release a variety of growth factors including GM-CSF and G-CSF (10)(11)(12). Second, although IL-1 by itself is incapable of supporting hemopoietic colony formation, in the murine system it has been found to greatly enhance the abilities of the different CSFs to support colony formation by primitive pluripotent stem cells (13)(14)(15)(16).…”

A role for manganese superoxide dismutase in radioprotection of hematopoietic stem cells by interleukin-1

“…Figure 6 shows one of three similar experiments in which pretreatment of K562 cells with I L l was shown to have no effect on the growth characteristics in both the unirradiated and irradiated groups. No protective effects of ILI were seen for K562 cells at 6 or 8 C y (Fig 6) nor when lower radiation doses were used (data not shown).…”