THE REGULATION OF HEMATOPOIESIS IN MAX-41 TRANSGENIC MICE WITH SUSTAINED EXCESS GRANULOPOIESIS

max 41 transgenic mice consistently exhibit elevated numbers of mature granulocytes and monocytes in the peripheral blood and of immature an d mature cells of these lineages in the marrow, spleen, lymph nodes an d liver. The immature populations are not autonomous and exhibit a nor mal quantitative responsiveness to proliferative stimulation by the fo ur colony-stimulating factors. The present studies examined three othe r candidate regulators of granulocyte formation and showed that max 41 cells exhibit normal quantitative responsiveness to stem cell factor, slightly enhanced responsiveness to IL-6 but reduced responsiveness t o Flk-ligand. Serum levels of growth factors were not unusually elevat ed in max 41 mice before or after the injection of endotoxin nor were excessive levels of the four CSFs or IL-6 produced in cultures of max 41 organs. Responses to injected G-CSF were not unusually high in term s of fold-elevations in max 41 mice. Levels of mRNA for various growth factors were not abnormal in max 41 marrow populations although, in c rowded cultures, max 41 marrow cells exhibited a higher level of endog enously stimulated colony formation than control cells. max 41 cells a lso exhibited elevated responsiveness to stimulation by mixtures of gr owth factors, particularly those in organ-conditioned media. The prese nt observations suggest some possible mechanisms by which a max 41 mou se might achieve a sustained elevation of granulocyte and monocyte pro duction but the data seem insufficient to provide a complete explanati on and indicate persisting deficiencies in knowledge of how granulocyt e and monocyte production is regulated.