RESPONSIVENESS OF HEMATOPOIETIC TISSUE TO ERYTHROPOIETIN IN RELATION TO THE TIME OF ADMINISTRATION AND DURATION OF ACTION OF THE HORMONE.

Following the injection of erythropoietin either in a single large dose or in multiple doses, a change in the responsiveness of the hematopoietic tissue occurs. The fact that different doses of erythropoietin stimulate erythropoiesis to the same extent when the action of the hormone is limited to 6 hours by the injection of antibody suggests that the stem cells are receptive to the action of erythropoietin only at some limited time in their individual life cycle. It is suggested that this period is sometime after metaphase and before the commencement of DNA synthesis in the interphase state of individual stem cells. It is further suggested that the increased responsiveness of the hematopoietic tissue to erythropoietin following injection is due to recruitment of stem cells into this receptive state. This recruitment may be due to both the division of stem cells and the movement of cells through cell cycle into the receptive state. The results are discussed in relation to two recent models of stem cell kinetics.

[1]  E. McCulloch,et al.  THE EFFECT OF ERYTHROPOIETIC STIMULATION ON THE HEMOPOIETIC COLONY-FORMING CELLS OF MICE. , 1964, Blood.

[2]  J. Schooley,et al.  Immunological Neutralization of Various Erythropoietins.∗ , 1963, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[3]  J. Lingrel,et al.  Synthesis of HÆmoglobin in Relation to the Maturation of Erythroid Cells , 1962, Nature.

[4]  L. Lajtha,et al.  Kinetic Model of a Bone‐Marrow Stem‐Cell Population , 1962, British journal of haematology.

[5]  L. Lajtha,et al.  A Method for Investigation of Stern‐Cell Kinetics , 1962 .

[6]  C. Gurney,et al.  Studies on erythropoiesis. XVII. Some quantitative aspects of the erythropoietic response to erythropoietin. , 1961, Blood.

[7]  D. V. Van Dyke,et al.  Response of Rats of Various Ages to Erythropoietin.∗ , 1961, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[8]  A. Erslev,et al.  The effect of anemic anoxia on the cellular development of nucleated red cells. , 1959, Blood.

[9]  E. Alpen,et al.  OBSERVATIONS ON REGULATION OF ERYTHROPOIESIS AND ON CELLULAR DYNAMICS BY Fe$sup 59$ AUTORADIOGRAPHY , 1959 .

[10]  C. Gurney,et al.  Studies on Erythropoiesis IX. Mechanism of Decreased Erythropoiesis In Experimental Polycythemia , 1958, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[11]  E E OSGOOD,et al.  A unifying concept of the etiology of the leukemias, lymphomas, and cancers. , 1957, Journal of the National Cancer Institute.

[12]  A. Erslev,et al.  Humoral regulation of red cell production. , 1953, Blood.

[13]  J. Till,et al.  A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Gurney Cw,et al.  Effect of Radiation on the Mouse Stem Cell Compartment in Vivo , 1963 .

[15]  L. Lajtha,et al.  A method for investigation of stem-cell kinetics. , 1962, British journal of haematology.

[16]  T. Krzymowski,et al.  Studies on the erythropoiesis inhibiting factor in the plasma of animals with transfusion polycythemia. , 1962, Blood.

[17]  C. Gurney,et al.  Studies on erythropoiesis. XVI. Response to a single dose of erythropoietin in polycythemic mouse. , 1961, The Journal of laboratory and clinical medicine.