Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow precursors: importance of accessory cells

Abstract

Recently, human multi-CSF was obtained by molecular cloning. In the present study, the effects of multi-CSF in vitro were investigated by comparative culture of whole bone marrow or progenitor cells obtained by sorting the cell fraction that binds the monoclonal antibody (MoAb) B13C5 (CD 34). Multi-CSF stimulated erythroid (BFU-E), multipotential (CFU-GEMM) and eosinophil (CFU-Eo) colonies in cultures of the progenitor cell enriched fraction, whereas (besides BFU-E, CFU-GEMM, and CFU-Eo) granulocyte (CFU-G), granulocyte-macrophage (CFU-GM), and macrophage (CFU-M) colony-forming cells also were stimulated by multi-CSF when unfractionated bone marrow was cultured. Reconstitution of the progenitor cell fraction (B13C5 positive) with the B13C5-negative population restored the broad spectrum of progenitor cell stimulation. This suggested that accessory cells are required for expression of the full spectrum of progenitor cell stimulation by multi-CSF. Subsequently, specific marrow cell populations, including T lymphocytes, granulocytic cells, and monocytes, were prepared by using selected MoAbs in complement-mediated lysis or cell sorting, added to cultures of hematopoietic progenitors and tested for accessory cell function. The results demonstrate that small numbers of monocytes permit the stimulation of CFU-G, CFU-GM, and CFU-M by multi-CSF. These monocyte-dependent stimulating effects on CFU-G, CFU-GM, and CFU-M could also be achieved by adding recombinant GM-CSF as a substitute for monocytes to the cultures. Therefore, multi-CSF most likely has direct stimulative effects on BFU-E, CFU-GEMM, and CFU-Eo and indirect effects on CFU-G, CFU-GM, and CFU-M in the presence of monocytes.