Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Ultrastructural changes of bone marrow in canine cyclic hematopoiesis (CH dog)

A sequential study

  • 31 Accesses

  • 11 Citations

Summary

The pathogenesis of cyclic hematopoiesis (CH) in the grey collie dog is still unknown. It has been proposed that periodic bursts of necrosis of the bone marrow neutrophils would induce cyclic arrests of the stem cell differentiation. In the present study, the sequential changes undergone by the erythroid and neutrophil series of the bone marrow of CH dogs were evaluated by electron microscopy. Erythroid cells presented quantitative periodic oscillations but the morphologic features of both immature and mature cells were normal. On the contrary, nonspecific necrotic changes were observed to occur in the myeloid series. Those abnormalities, which were more marked between days 9 and 11 of the cycle, mainly involved the immature cells and, to a lesser extent, the mature neutrophils. The number of necrotic cells was variable in different cycles, but always represented a small portion of the myeloid cells. In addition, few bone marrow macrophages displayed signs of phagocytic activity containing cell debris. The ultrastructural changes of the myeloid series were accompanied by an abnormal decrease of peroxidase activity and the permanence of large acid phosphatase-positive Golgi complexes in mature neutrophils, as defined by morphologic criteria. Döhle-like arrays of rough endoplasmic reticulum were present in many cells. Our findings suggest that an asynchronic development of myelocytes occurs as a result of regulatory abnormalities related to the congenital defect of the bone marrow which interferes with the differentiation and maturation of the stem cells. Necrosis in some myeloid cells would be a secondary phenomenon rather than a causal factor for the cyclic arrest of cell maturation as has been previously submitted. Furthermore, the small size of the necrotic cell population could not justify the production of “inhibitors” in sufficient amounts as to block the normal evolution of the bone marrow stem cell pool.

This is a preview of subscription content, log in to check access.

References

  1. Ackerman GA (1968) Ultrastructure and cytochemistry of the developing neutrophil. Lab Invest 19:290–302

  2. Adamson JW, Dale DC, Elin RJ (1974) Hematopoiesis in the grey collie dog. Studies of the regulation of erythropoiesis. J Clin Invest 54:965–973

  3. Beard ME, Novikoff AB (1969) Distribution of peroxisomes (microbodies) in the nephron of the rat. A cytochemical study. J Cell Biol 42:501–518

  4. Cawley JC, Hayhoe FGJ (1972) The inclusions of the May-Hegglin anomaly and Döhle bodies of infection: an ultrastructural comparison. Br J Haemtol 22:491–496

  5. Cawley JC, Hayhoe FGJ (1973) Ultrastructure of haemic cells. In: A cytological atlas of normal and leukaemic blood and bone marrow. WB Saunders Co, Ltd, London, p 55

  6. Cheville NF (1968) Amyloidosis associated with cyclic neutropenia in the dog. Blood 31:111–114

  7. Cheville NF, Cutlip RC, Moon HW (1970) Microscopic pathology of the gray collie syndrome. Cyclic neutropenia, amyloidosis, enteritis, and bone necrosis. Pathol Vet 7:225–245

  8. Dale DC, Alling CW, Wolff SM (1972) Cyclic hematopoiesis: the mechanism of cyclic neutropenia in grey collie dogs. J Clin Invest 51:2197–2204

  9. Dale DC, Brown CH, Carbone P, Wolff SM (1971) Cyclic urinary leukopoietic activity in grey collie dogs. Science 173:152–153

  10. Dale DC, Graw RG Jr (1974) Transplantation of allogeneic bone marrow in canine cyclic neutropenia. Science 183:83–84

  11. Dale DC, Ward SB, Kimball HR, Wolff SM (1972) Studies of neutrophil production and turnover in grey collie dogs with cyclic neutropenia. J Clin Invest 46:1932–1942

  12. Fedorko M (1967) Effect of chloroquine on morphology of cytoplasmic granules in maturing human leukocytes — an ultrastructural study. J Clin Invest 46:1932–1942

  13. Ford L (1969) Hereditary aspects of human and canine cyclic neutropenia. J Hered 60:293–299

  14. Gregory RS, Machado EA, Jones JB (1977) Animal model of human disease. Amyloidosis. Am J Pathol 87:721–724

  15. Itoga T, Laszlo J (1962) Döhle bodies and other granulocytic alterations during chemotherapy with cyclophosphamide. Blood 20:668–674

  16. Jones JB, Lange RD, Jones ES (1975) Cyclic hematopoiesis in a colony of dogs. J Am Vet Med Assoc 166:365–367

  17. Jones, JB, Yang TJ, Dale JB, Lange RD (1975) Canine cyclic hematopoiesis: marrow transplantation between littermates. Br J Haematol 30:215–233

  18. Lange RD, Jones JB: Canine cyclic hematopoiesis. In: Shifrine M, Wilson FD, (eds), Canine as a bio-medical research model: immunohematologic aspects. Washington, DC: US Department of Energy, Division of Technical Information (in press)

  19. Lange RD, Jones JB (1976) Hormonal control of erythropoiesis in canine cyclic haematopoiesis. Scand J Haematol 16:56–65

  20. Lund JE, Padgett GA, Gorham JR (1970) Additional evidence on the inheritance of cyclic neutropenia in the dog. J Hered 61:47–49

  21. Lund JE, Padgett GA, Ott RL (1967) Cyclic neutropenia in grey collie dogs. Blood 29:452–461

  22. Machado EA, Gregory RS, Jones JB, Lange RD (1978) The cyclic hematopoietic dog: a model for spontaneous secondary amyloidosis. A morphologic study. Am J Pathol 92:23–34

  23. Machado EA, Jones JB, Lange RD (1979) Ultrastructural studies on the evolution of amyloidosis in the cyclic hematopoietic (CH) dog. Virchows Arch [Pathol Anat] 383:167–179

  24. Novikoff PM, Novikoff AB, Quintana N, Nauw J-J (1971) Golgi apparatus, GERL, and lysosomes of neurons in rat dorsal root ganglia, studied by thick section and thin section cytochemistry. J Cell Biol 50:859–886

  25. Parmley RT, Ogawa M, Darby CP Jr, Spicer SS (1975) Congenital neutropenia: neurophil proliferation with abnormal maturation. Blood 46:723–745

  26. Scott RE, Dale DC, Rosenthal AS (1973) Cyclic neutropenia in grey collie dogs. Ultrastructural evidence for abnormal neutrophil granulopoiesis. Lab Invest 28:514–525

  27. Spicer SS, Hardin JH (1969) Ultrastructure, cytochemistry, and function of neutrophil leukocyte granules. A review. Lab Invest 20:488–497

  28. Weiden PL, Robinett B, Graham TC, Adamson J, Storb R (1974) Canine cyclic neutropenia: a stem cell defect. J Clin Invest 53:950–953

  29. Yang TJ, Jones JB, Jones ES, Lange RD (1974) Serum colony-stimulating activity of dogs with cyclic neutropenia. Blood 44:41–48

Download references

Author information

Correspondence to E. A. Machado M.D..

Additional information

This study was supported by Grants NIH RR00874, HL15647, and FR5541, from the National Institutes of Health, DHHS

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Machado, E.A., Jones, J.B., Aggio, M.C. et al. Ultrastructural changes of bone marrow in canine cyclic hematopoiesis (CH dog). Virchows Arch. A Path. Anat. and Histol. 390, 93–108 (1981). https://doi.org/10.1007/BF00443900

Download citation

Key words

  • Cyclic hematopoiesis
  • Bone marrow
  • Ultrastructure
  • Nuclearcytoplasmic asynchrony
  • Döhle-like bodies