The long-term goal of the proposed research is to establish that uteroferrin (UF), a progesterone-induced acid phosphatase from pig uterus (UF) and a Type 5 acid phosphatase from human placenta (human UF, hUF), are hematopoietic growth factors. Using in vitro colony forming unit assays with nonadherent hematopoietic stem cells from bone marrow and peripheral blood, UF and hUF will be tested for erythroid (CFU-E), granulocyte-monocyte/macrophage (CFU-GM) and granulocyte-erythroid-monocyte/macrophage-megakaryocyte (CFU-GEMM) activities. The biochemical components of UF and hUF required for hematopoietic activity, especially iron, will. be determined. Site directed mutagenesis will be used to determine functional domains of UF required for iron binding and for hematopoietic growth factor activity. Hematopoietic growth factor activities of UF from pig uterus and human term placenta will be compared. Effects of UF on proliferating hematopoietic progenitor cells from peripheral blood and bone marrow, as well as from more primitive nonproliferating hematopoietic progenitor cells (CD 34+/CD 33-cells) isolated from peripheral blood and bone marrow of pigs following treatment with the myelosuppressive drug 5 fluorouracil will be evaluated using combinations of suspension cultures and methylcellulose cultures in the presence and absence of recombinant human erythropoietin, granulocyte/monocyte colony stimulating factor and interleukin 3. Receptors for UF on these two populations (proliferating and more primitive CD34+/CD33-) of hematopoietic progenitor cells will be compared. Effects of in vivo administration of exogenous UF on spleen weights, blood volume, bone marrow volume, differential blood cell counts and total hematopoietic stem cells in liver, spleen and bone marrow of weaned pigs will also be determined. Results of these studies will elucidate the mechanisms involved in the hematopoietic growth factor activity of UF and indicate structural and functional aspects of UF required for this activity.
| Laurenz, J C; Hadjisavas, M; Chovanic, G W et al. (1997) Myelosuppression in the pig (Sus scrofa): uteroferrin reduces the myelosuppressive effects of 5-fluorouracil in young pigs. Comp Biochem Physiol A Physiol 116:369-77 |
| Laurenz, J C; Hadjisavas, M; Schuster, D et al. (1997) The effect of uteroferrin and recombinant GM-CSF on hematopoietic parameters in normal female pigs (Sus scrofa). Comp Biochem Physiol B Biochem Mol Biol 118:579-86 |
| Laurenz, J C; Hadjisavas, M; Schuster, D et al. (1997) Uteroferrin and recombinant bovine GM-CSF modulate the myelosuppressive effects of 5-fluorouracil in young female pigs (Sus scrofa). Comp Biochem Physiol B Biochem Mol Biol 118:569-77 |
| Tuo, W; Harney, J P; Bazer, F W (1995) Colony-stimulating factor-1 in conceptus and uterine tissues in pigs. Biol Reprod 53:133-42 |
