Murine myeloid progenitor responses to GM-CSF and eosinophil precursor responses to IL-5 represent distinct targets for downmodulation by prostaglandin E2

Abstract

1. Because Prostaglandin E2 (PGE2) and dibutiryl cyclic AMP (dbcAMP) modulate the production and effects of haemopoietic cytokines in allergy, we examined their ability to modulate responses of myeloid progenitors to GM-CSF, and of eosinophil precursors to IL-5. 2. The ability of PGE2, dbcAMP, rolipram, forskolin, dbcGMP and PGD2, to modulate the responses to GM-CSF and IL-5 in colony formation (progenitor) and eosinophil differentiation (precursor) assays using bone-marrow from nonsensitized or from intranasally-challenged, ovalbumin-sensitized mice of five strains was studied. 3. PGE2 (10-7 M) inhibited GM-CSF-stimulated colony formation in bone-marrow from BP-2 mice. This effect was duplicated by dbcAMP (0.3 - 1 x 10-6 M), Rolipram (10-5 M) and forskolin (3 x 10-5 M), but not Prostaglandin D2 (10-6 M). Inhibition affected similarly all myeloid colony types. Progenitors from sensitized and challenged BP-2 mice were also inhibited by PGE2 and cyclic AMP. PGE2 inhibited progenitors from C57BL/10, CBA/J and A/J, but not BALB/c mice. However, BALB/c progenitors were sensitive to dbcAMP and Forskolin (10-4 M). In contrast, in precursor assays, PGE2 (10-7-10-9 M) blocked responses to IL-5 in bone-marrow from BP-2 and BALB/c mice, either naive or sensitized and challenged, to a similar extent. PGD2 (10-6 M) was ineffective, as was PGE2 (10-7 M), if added after 48 h of culture. 4. In conclusion, PGE2 inhibits the responses of bone-marrow myeloid progenitors to GM-CSF and of eosinophil precursors to IL-5, in naive or ovalbumin sensitized and challenged mice. These effects are duplicated by cyclic AMP-elevating agents. In the BALB/c strain, the resistance of progenitors, but not precursors, to PGE2 inhibition, indicates these developmental stages are separate targets for PGE2 modulation.