Effects of B cell stimulatory factor-1/interleukin 4 on hematopoietic progenitor cells

Abstract

B cell stimulatory factor-1 (BSF-1)/Interleukin 4 (IL 4) is a T cell product originally characterized on the basis of its actions on B lymphocytes. Recently it has been reported that BSF-1 activates T cell and mast cell lines. We now provide evidence that BSF-1, purified to homogeneity, also has a broad spectrum of activity on hematopoietic progenitor cells (HPC). However, like its action on B cells, prolierative effects were only observed when BSF-1 was combined with an additional factor. Thus BSF-1, in costimulation with recombinant G-CSF, enhances the proliferation of granulocyte-macrophage progenitor cells (CFU-GM). BSF-1 increases the proliferation of CFU-e in the presence of recombinant erythropoietin (rEPO). Furthermore, BSF-1 induces, together with rEPO, colony formation by primitive erythroid (BFU-e) and multipotent (CFU-mix) progenitor cells comparable to that observed with rEPO and interleukin 3 (IL 3). BSF-1 is also active as a megakaryocyte colony-stimulating factor; in combination with recombinant interleukin 1, rEPO or the supernatant of the T cell hybridoma FS7–20.6.18, BSF-1 induces megakaryocyte colony formation (CFU-Mk). The same factors that synergize with BSF-1 also enhance CFU-Mk proliferation induced by IL 3. Although the precise mechanisms of action of BSF-1 on HPC is not yet known, we propose that BSF-1 represents an activation factor for HPC and prepares the progenitor cells to respond to specific growth or differentiation factors.

Increased numbers of committed myeloid progenitors but not primitive hematopoietic stem/progenitors in mice lacking STAT6 expression

“…IL-4R can be found on mature T and B lymphocytes, macrophages, and blast-like hematopoietic cell lines [35]. In addition to the classical B lymphocyte stimulatory activity, at the progenitor cell level, IL-4 costimulation synergizes with G-CSF to promote granulocyte-colony formation, with EPO effects on BFU-E and megakaryocytopoiesis by IL-3 [36,37]. Furthermore, the combination of IL-4 and IL-11 has been reported to stimulate more primitive, multipotential blast-cell colonies [38].…”

Interferon-α and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells

“…IL-4 antagonizes the protective effect of IFN-␣ against viral infection of fibroblasts, and inhibits the IFN-␣-induced transcription of the ISG-54 gene by monocytes [43,44]. Finally, IFN-␣ and IL-4 have opposing effects on hematopoiesis: IFN-␣ inhibits the proliferation of multipotent, granulocyte-macrophage, erythroid and megakaryocyte progenitor cells, whereas IL-4 acts in concert with other growth factors to promote the growth of multiple hematopoietic lineages [45][46][47][48][49][50][51][52][53][54][55][56]. However, IL-4 inhibits macrophage progenitor proliferation in vitro [55][56][57].…”

Action of human interleukin‐4 and stem cell factor on erythroid and mixed colony formation by peripheral blood‐derived CD34+c‐kithigh or CD34+c‐kitlow cells

“…Interleukin (IL)-4 is a unique cytokine, which may have a dual regulatory function in haemopoiesis (Vellenga et al, 1993;Ferrajoli et al, 1993;Sonoda, 1994). It additively or synergistically promotes the proliferation and differentiation of progenitor cells with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo) (Peschel et al, 1987;Rennick et al, 1987;Broxmeyer et al, 1988;Sonoda et al, 1990;Vellenga et al, 1990;Snoeck et al, 1993a, b). In contrast, it inhibits macrophage colony formation supported by IL-3 plus macrophage (M)-CSF, by granulocyte/macrophage (GM)-CSF, or by M-CSF ( Jansen et al, 1989;Sonoda et al, 1990;Vellenga et al, 1990).…”

“…Several investigators (Peschel et al, 1987;Migliaccio et al, 1989;De Wolf et al, 1990 have obtained conflicting results concerning the effects of IL-4 on erythropoiesis. Peschel et al (1987) first reported that murine IL-4 (mIL-4) augments erythroid colony formation from early and late erythroid progenitors (BFU-E and CFU-E) in the presence of Epo. However, they used relatively high-density cultures (2-4 × 10 4 bone marrow (BM) cells/0 .…”