INCREASED G-CSF RESPONSIVENESS OF BONE-MARROW CELLS FROM HEMATOPOIETIC-CELL PHOSPHATASE DEFICIENT VIABLE MOTH-EATEN MICE

The mouse mutation viable motheaten (me(nu)) results in defects in the expression and catalytic activity of the cytoplasmic protein tyrosine phosphatase known as hematopoietic cell phosphatase (HCP). This reduc tion in HCP activity leads to the aberrant regulation of several myelo id and lymphoid cell lineages, including substantial increases in numb ers of granulocytes. The differentiation, proliferation, and survival of cells in this lineage are normally supported by granulocyte-colony stimulating factor (G-CSF). Tn this study we have determined the conse quences of the loss of HCP activity in me(nu)/me(nu) mice on the respo nse of bone marrow cells to G-CSF. Bone marrow from these mice exhibit ed substantial increases in clonogenic and proliferative responses to G-CSF. These enhanced activities of G-CSF correlated with an increase in the level of immature granulocytic, G-CSF receptor positive cells i n the bone marrow. These results suggested the possibility that HCP ma y regulate the G-CSF receptor by a direct interaction. However, under conditions where the previously described interaction between the eryt hropoietin receptor and HCP was readily observed, HCP did not detectab ly associate with the G-CSF receptor.