Abstract
Hematopoiesis in the grey collie dog undergoes periodic fluctuations which involve reticulocytes, granulocytes, platelets, lymphocytes, and monocytes. This syndrome is inherited in an autosomal recessive manner and can be transmitted or abolished by appropriate bone marrow transplantation experiments, thus demonstrating this to be a primary marrow defect. Investigation of humoral regulation in this setting indicates that serum erythropoietin (ESF) also undergoes cyclic fluctuation and that shortly after the increase and peak in serum ESF levels recognizable red cell precursors appear in the marrow. Erythropoiesis in the grey collie is reciprocally related to the blood O2 carrying capacity. With phlebotomy, ESF activity and reticulocytes increase but continue to cycle, while hypertransfusion eliminates reticulocyte production completely. Neither phlebotomy nor hypertransfusion alter the underlying cycle time (11-12 days) nor influence the peaks of peripheral blood granulocytes. Thus, in these experiments, no direct evidence of competition between reticulocyte and granulocyte production is observed. In vitro studies of canine hemoglobin synthesis fail to demonstrate evidence of an inhibitor to ESF. These results indicate that periodic fluctuation of serum ESF is an integral part of the grey collie syndrome and are most consistent with some form of feedback regulation of ESF production.
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Selected References
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- Adamson J. W. The erythropoietin-hematocrit relationship in normal and polycythemic man: implications of marrow regulation. Blood. 1968 Oct;32(4):597–609. [PubMed] [Google Scholar]
- Alexanian R. Erythropoietin excretion in bone marrow failure and hemolytic anemia. J Lab Clin Med. 1973 Sep;82(3):438–445. [PubMed] [Google Scholar]
- Bozzini C. E. Influence of the erythroid activity of the bone marrow on the plasma disappearance of injected erythropoietin in dogs. Nature. 1966 Mar 12;209(5028):1140–1141. doi: 10.1038/2091140b0. [DOI] [PubMed] [Google Scholar]
- Dale D. C., Alling D. W., Wolff S. M. Cyclic hematopoiesis: the mechanism of cyclic neutropenia in grey collie dogs. J Clin Invest. 1972 Aug;51(8):2197–2204. doi: 10.1172/JCI107027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dale D. C., Brown C. H., Carbone P., Wolff S. M. Cyclic urinary leukopoietic activity in gray collie dogs. Science. 1971 Jul 9;173(3992):152–153. doi: 10.1126/science.173.3992.152. [DOI] [PubMed] [Google Scholar]
- Dale D. C., Graw R. G., Jr Transplantation of allogenic bone marrow in canine cyclic neutropenia. Science. 1974 Jan 11;183(4120):83–84. doi: 10.1126/science.183.4120.83. [DOI] [PubMed] [Google Scholar]
- Dale D. C., Ward S. B., Kimball H. R., Wolff S. M. Studies of neutrophil production and turnover in grey collie dogs with cyclic neutropenia. J Clin Invest. 1972 Aug;51(8):2190–2196. doi: 10.1172/JCI107026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Finne P. H., Skoglund R., Wetterhus S. Urinary erythropoietin excretion during initial treatment of pernicious anaemia. Scand J Haematol. 1973;10(1):62–68. doi: 10.1111/j.1600-0609.1973.tb00041.x. [DOI] [PubMed] [Google Scholar]
- Fried W., Johnson C., Heller P. Observations on regulation of erythropoiesis during prolonged periods of hypoxia. Blood. 1970 Nov;36(5):607–616. [PubMed] [Google Scholar]
- Hammond D., Shore N., Movassaghi N. Production, utilization and excretion of erythropoietin. I. Chronic anemias. II. Aplastic crisis. 3. Erythropoietic effects of normal plasma. Ann N Y Acad Sci. 1968 Mar 29;149(1):516–527. doi: 10.1111/j.1749-6632.1968.tb15191.x. [DOI] [PubMed] [Google Scholar]
- Hellman S., Grate H. E. Haematopoietic stem cells: evidence for competing proliferative demands. Nature. 1967 Oct 7;216(5110):65–66. doi: 10.1038/216065a0. [DOI] [PubMed] [Google Scholar]
- KRANTZ S. B., GALLIEN-LARTIGUE O., GOLDWASSER E. THE EFFECT OF ERYTHROPOIETIN UPON HEME SYNTHESIS BY MARROW CELLS IN VITRO. J Biol Chem. 1963 Dec;238:4085–4090. [PubMed] [Google Scholar]
- Lawrence J. S., Craddock C. G., Jr Stem cell competition: the response to antineutrophilic serum as affected by hemorrhage. J Lab Clin Med. 1968 Nov;72(5):731–738. [PubMed] [Google Scholar]
- Lund J. E., Padgett G. A., Ott R. L. Cyclic neutropenia in grey collie dogs. Blood. 1967 Apr;29(4):452–461. [PubMed] [Google Scholar]
- Miller M. E., Rorth M., Parving H. H., Howard D., Reddington I., Valeri C. R., Stohlman F., Jr pH effect on erythropoietin response to hypoxia. N Engl J Med. 1973 Apr 5;288(14):706–710. doi: 10.1056/NEJM197304052881404. [DOI] [PubMed] [Google Scholar]
- Morley A., Stohlman F., Jr Cyclophosphamide-induced cyclical neutropenia. An animal model of a human periodic disease. N Engl J Med. 1970 Mar 19;282(12):643–646. doi: 10.1056/NEJM197003192821202. [DOI] [PubMed] [Google Scholar]
- Morley A., Stohlman F., Jr Erythropoiesis in the dog: the periodic nature of the steady state. Science. 1969 Sep 5;165(3897):1025–1027. doi: 10.1126/science.165.3897.1025. [DOI] [PubMed] [Google Scholar]
- Naets J. P., Wittek M. Effect of erythroid hyperplasia on utilization of erythropoietin. Nature. 1965 May 15;206(985):726–727. doi: 10.1038/206726a0. [DOI] [PubMed] [Google Scholar]
- Patt H. M., Lund J. E., Maloney M. A. Cyclic hematopoiesis in grey collie dogs: a stem-cell problem. Blood. 1973 Dec;42(6):873–884. [PubMed] [Google Scholar]
- SCHADE A. L., OYAMA J., REINHART R. W., MILLER J. R. Bound iron and unsaturated iron-binding capacity of serum; rapid and reliable quantitative determination. Proc Soc Exp Biol Med. 1954 Nov;87(2):443–448. doi: 10.3181/00379727-87-21407. [DOI] [PubMed] [Google Scholar]
- SCHOOLEY J. C., GARCIA J. F. SOME PROPERTIES OF SERUM OBTAINED FROM RABBITS IMMUNIZED WITH HUMAN URINARY ERYTHROPOIETIN. Blood. 1965 Feb;25:204–217. [PubMed] [Google Scholar]
- STOHLMAN F., Jr, BRECHER G. Humoral regulation of erythropoiesis. V. Relationship of plasma erythropoietine level to bone marrow activity. Proc Soc Exp Biol Med. 1959 Jan;100(1):40–43. doi: 10.3181/00379727-100-24516. [DOI] [PubMed] [Google Scholar]
- STOHLMAN F., Jr Erythropoiesis. N Engl J Med. 1962 Aug 23;267:392–concl. doi: 10.1056/NEJM196208232670806. [DOI] [PubMed] [Google Scholar]
- Siri W. E., Van Dyke D. C., Winchell H. S., Pollycove M., Parker H. G., Cleveland A. S. Early erythropoietin, blood, and physiological responses to severe hypoxia in man. J Appl Physiol. 1966 Jan;21(1):73–80. doi: 10.1152/jappl.1966.21.1.73. [DOI] [PubMed] [Google Scholar]
- Stohlman F., Quesenberry P. J. Colony-stimulating factor and myelopoiesis. Blood. 1972 May;39(5):727–732. [PubMed] [Google Scholar]
- Ward H. P. An in vitro assay of erythropoietin. Proc Soc Exp Biol Med. 1967 Jun;125(2):370–374. doi: 10.3181/00379727-125-32094. [DOI] [PubMed] [Google Scholar]
- Wardle D. F., Malpas J. S., Wrigley P. F. Bioassay of erythropoietin using foetal mouse liver cells. Br J Haematol. 1973 Jan;24(1):49–56. doi: 10.1111/j.1365-2141.1973.tb05726.x. [DOI] [PubMed] [Google Scholar]
- Weiden P. L., Robinett B., Graham T. C., Adamson J., Storb R. Canine cyclic neutropenia. A stem cell defect. J Clin Invest. 1974 Mar;53(3):950–953. doi: 10.1172/JCI107636. [DOI] [PMC free article] [PubMed] [Google Scholar]