Thrombopoietin accelerates platelet, red blood cell, and neutrophil recovery in myelosuppressed mice.
The recent cloning of thrombopoietin (TPO) has allowed us to study its in vivo effects in normal and myelosuppressed mice. Normal Balb/c mice were treated with recombinant human TPO (hTPO) at doses ranging from 1 to 20 kU for 7 days, and complete blood counts (CBCs) and the number of megakaryocytes in the bone marrow were determined. Platelet counts were increased starting on day 5 after mice were treated with hTPO. Platelet counts reached a peak between days 8 and 11 and returned to baseline between days 16 and 20. hTPO treatment increased the number of megakaryocytes in the bone marrow starting on day 3. In normal mice, hTPO treatment did not affect red or white blood cell (RBC or WBC) counts. To test the effects of hTPO in myelosuppressed mice, Balb/c mice were irradiated with 350 cGy total-body irradiation and dosed with 1.2 mg carboplatin, resulting in severe and prolonged thrombocytopenia, anemia, and neutropenia. Treatment with 5-20 kU hTPO for 7 days accelerated the recovery of platelet, RBC, and neutrophil counts in myelosuppressed mice and also significantly improved their nadirs. In addition, bone marrow megakaryocyte numbers recovered 11 days earlier and reticulocyte counts recovered 10 days earlier in hTPO-treated myelosuppressed mice than in controls. These results indicate that TPO can improve hematopoietic recovery in myelosuppressed mice, affecting multiple cell lineages.
Grossmann
A
A
ZymoGenetics Inc., Seattle, WA, USA.
Lenox
J
J
Ren
H P
HP
Humes
J M
JM
Forstrom
J W
JW
Kaushansky
K
K
Sprugel
K H
KH
D000740:Anemia; D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D016190:Carboplatin / Q000633:toxicity; D004912:Erythrocytes / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012156:Reticulocytes / Q000166:cytology / Q000187:drug effects; D013921:Thrombocytopenia; D013926:Thrombopoietin / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D011994:Recombinant Proteins; D013926:Thrombopoietin; D016190:Carboplatin