Modification of splenic megakaryocytopoiesis in sublethally irradiated mice by a thrombocytopoiesis-stimulating factor

Author

Ronnie Wayne Culberson

Date of Award

5-1992

Degree Type

Thesis

Degree Name

Master of Science

Major

Comparative and Experimental Medicine

Major Professor

T. W. Schultz

Committee Members

Ted P. McDonald, John R. Kennedy

Abstract

The radioprotective effects of TSF (thrombocytopoiesis-stimulating factor or thrombopoietin) have been studied in irradiated mice in relation to bone marrow megakaryocytopoiesis, but not splenic megakaryocytopoiesis. The work reported here was undertaken to determine the effects of TSF on splenic megakaryocytopoiesis in mice exposed to 3.0 Gy of ¹³⁷Cs. Mice were given Step II TSF 1 hour before and 8 hours after whole-body irradiation for a total of 4 U of TSF per mouse. For controls, additional mice were injected with human serum albumin (HSA), normal rabbit serum (NRS), or rabbit anti-mouse platelet serum (RAMPS). Blood was collected from each mouse on days 10 and 14 after irradiation for measurement of platelet counts, %³⁵S incorporations into platelets, platelet sizes, packed cell volumes (PCV), RBC counts, and WBC counts. Spleens were removed and processed for measurement of megakaryocyte size and number. Severe thrombocytopenia and leukopenia were observed on days 10 and 14, but severe anemia was not present on either day. TSF caused significant increases in platelet count (P < 0.005), %³⁵S incorporation into platelets (P < 0.025) and WBC count (P < 0.005) on day 10 as compared to the values of mice treated with HSA. Similarly on day 10, RAMPS caused significant increases above NRS-treated mice in platelet count (P <0.005), %³⁵S incorporation into platelets (P < 0.0005), WBC count (P < 0.05), platelet size (P <0.0005) and PCV (P < 0.025). As compared to their irradiated controls, both TSF and RAMPS caused significant increases (P <0.0005) on day 10 in total megakaryocyte mass (TMM) and megakaryocyte number, but neither significantly increased megakaryocyte diameter on day 10. Neither TSF nor RAMPS significantly increased the peripheral blood measurements, megakaryocyte numbers, or TMM on day 14 as compared to their irradiated controls. TSF significantly increased (P < 0.05) splenic megakaryocyte diameter above HSA controls on day 14. The present studies showed that TSF caused significant increases above irradiated control mice in platelet count, ³⁵S incorporation into platelets, splenic megakaryocyte number, and TMM on day 10, and caused significant increases in splenic megakaryocyte diameter on day 14. These results show that TSF is an effective radioprotective agent and could be helpful in elevating platelet production in patients subjected to chemotherapy or radiation treatments.

Recommended Citation

Culberson, Ronnie Wayne, "Modification of splenic megakaryocytopoiesis in sublethally irradiated mice by a thrombocytopoiesis-stimulating factor. " Master's Thesis, University of Tennessee, 1992.
https://trace.tennessee.edu/utk_gradthes/12086