Uteroferrin: a progesterone-induced hematopoietic growth factor of uterine origin

Uteroferrin is a purple progesterone-induced glycoprotein containing two molecules of iron per 35,000 molecular weight polypeptide, which has high amino acid sequence homology with Type 5 acid phosphatases from normal human placentae, from sera of patients with hairy cell leukemia, Gaucher's disease, and osteoporosis, as well as from normal spleens of pigs, cattle, rats, and mice. Results of the present study indicate that uteroferrin also has colony-forming unit (CFU) activity for committed erythroid (BFU-E) and granulocyte-monocyte/macrophage (CFU-GM) cell lines and exists as far back as the granulocyte, erythrocyte, monocyte/macrophage, megakaryocyte (CFU-GEMM) committed lineage. Uteroferrin exerts maximum CFU activities at 1 microgram/ml in serum-free culture medium with no supplemental iron (90 micrograms/ml ferric iron). However, when ferric iron concentration in medium was increased to 200 micrograms/ml, uteroferrin had maximum CFU activities at 100 pg/ml. Preincubation of uteroferrin with polyclonal antiserum or monoclonal antibody to uteroferrin effectively eliminated its CFU activities. Uteroferrin derived from human term placentae also exhibits BFU-E, CFU-GM, and CFU-GEMM activities. The mechanism by which uteroferrin stimulates proliferation and differentiation of primitive hematopoietic stem cells is unclear.