Production of Colony-Stimulating Factor (CSF) by Bone Marrow Cells Stimulated with Lipopolysaccharide (LPS) and Phorbol Esters

Abstract

Colony stimulating factors (CSF) are glycoproteins which regulate the proliferation and differentiation of committed hemopoietic stem cells into mature granulocytes and macrophages. Murine spleen cells are one of the best sources for CSF and bacterial lipopolysaccharides (LPS) are effective stimulants of these cells to generate CSF. The injection of LPS into mice is followed by a rapid increase of CSF in the serum (15,23,3), and addition of LPS to spleen cultures induces release of CSF into the supernatants (4). In a previous study (2), we reported that lipid A is the moiety of the LPS molecule which is responsible for the generation of CSF. In a recent study we have shown that some preparations of polysaccharides, obtained from LPS after carefully controlled hydrolytic conditions, can also induce the generation of CSF (19). By using the LPS-low responder strain of mice, C3H/HeJ, we analyzed the genetic control involved in LPS-induced generation of CSF (3) and interferon (5,8). CSF is generated by macrophages and lymphocytes stimulated with LPS (6). Employing adherent and non-adherent spleen cells from LPS-responsive mice and C3H/HeJ mice vie demonstrated that both subpopulations of cells are required for the generation of CSF by LPS. Moreover, LPS interacts with the adherent cells which release a soluble factor which in turn stimulates the non-adherent cells to release CSF (7). Interaction between adherent and non-adherent cells is also requiered in vivo; mice tolerent to LPS which do not generate CSF after a challenging injection of LPS, produce CFS when injected with a mixture of adherent and non-adherent spleen cells from non-tolerant mice prior to the challenging injection of LPS (27).