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. 1984 Aug;116(2):279–288.

Cyclic ultrastructural abnormalities in human cyclic neutropenia.

R T Parmley, G J Presbury, W C Wang, J Wilimas
PMCID: PMC1900534  PMID: 6205594

Abstract

The ultrastructure of neutrophils from two brothers with cyclic neutropenia was studied at various time intervals of the neutrophil cycle, which varied from 15 to 21 days. During the nonneutropenic portion (middle third) of the cycle, when the blood neutrophil counts approached normal, the majority of blood and marrow segmented neutrophils appeared morphologically normal, whereas marrow promyelocytes demonstrated increased autophagy with decreased condensation of primary granules. During the early neutropenic portion of the cycle (first third), increased autophagy and granule abnormalities persisted in promyelocytes, myelocytes, and the few segmented neutrophils present. During the late neutropenic portion (last third) of the cycle, which preceded neutrophil recovery, most promyelocytes appeared morphologically normal, whereas the few segmented neutrophils present frequently contained increased autophagic and/or heterophagic vacuoles and decreased cytoplasmic granules. Abundant neutrophil debris was present in marrow macrophages consistent with dysgranulopoiesis and intramedullary destruction of abnormal myeloid cells. Similar changes were not observed in monocytes, eosinophils, or basophils. These results demonstrate a cyclic insult which has its initial morphologic impact on the promyelocyte of patients with cyclic neutropenia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chusid M. J., Bujak J. S., Dale D. C. Defective polymorphonuclear leukocyte metabolism and function in canine cyclic neutropenia. Blood. 1975 Dec;46(6):921–930. [PubMed] [Google Scholar]
  2. Crist W. M., Parmley R. T., Holbrook C. T., Castleberry R. P., Denys F. R., Malluh A. Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency. Am J Hematol. 1980;9(1):89–107. doi: 10.1002/ajh.2830090110. [DOI] [PubMed] [Google Scholar]
  3. Fedorko M. E., Hirsch J. G., Cohn Z. A. Autophagic vacuoles produced in vitro. I. Studies on cultured macrophages exposed to chloroquine. J Cell Biol. 1968 Aug;38(2):377–391. doi: 10.1083/jcb.38.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fittschen C., Parmley R. T., Austin R. L., Crist W. M. Vicinal glycol-staining identifies secondary granules in human normal and Chédiak-Higashi neutrophils. Anat Rec. 1983 Mar;205(3):301–311. doi: 10.1002/ar.1092050307. [DOI] [PubMed] [Google Scholar]
  5. Ford L. Hereditary aspects of human and canine cyclic neutropenia. J Hered. 1969 Sep-Oct;60(5):293–299. doi: 10.1093/oxfordjournals.jhered.a107998. [DOI] [PubMed] [Google Scholar]
  6. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  7. Krance R. A., Spruce W. E., Forman S. J., Rosen R. B., Hecht T., Hammond W. P., Blume K. G. Human cyclic neutropenia transferred by allogeneic bone marrow grafting. Blood. 1982 Dec;60(6):1263–1266. [PubMed] [Google Scholar]
  8. Machado E. A., Jones J. B., Aggio M. C., Chernoff A. I., Maxwell P. A., Lange R. D. Ultrastructural changes of bone marrow in canine cyclic hematopoiesis (CH dog). A sequential study. Virchows Arch A Pathol Anat Histol. 1981;390(1):93–108. doi: 10.1007/BF00443900. [DOI] [PubMed] [Google Scholar]
  9. Mangalik A., Robinson W. A. Cyclic neutropenia: the relationship between urine granulocyte colony stimulating activity and neutrophil count. Blood. 1973 Jan;41(1):79–84. [PubMed] [Google Scholar]
  10. Meuret G., Fliedner T. M. Neutrophil and monocyte kinetics in a case of cyclic neutropenia. Blood. 1974 Apr;43(4):565–571. [PubMed] [Google Scholar]
  11. PAGE A. R., GOOD R. A. Studies on cyclic neutropenia; a clinical and experimental investigation. AMA J Dis Child. 1957 Dec;94(6):623–661. doi: 10.1001/archpedi.1957.04030070035006. [DOI] [PubMed] [Google Scholar]
  12. Parmley R. T., Crist W. M., Ragab A. H., Boxer L. A., Malluh A., Findley H. Phagocytosis of neutrophils by marrow macrophages in childhood chronic benign neutropenia. J Pediatr. 1981 Feb;98(2):207–212. doi: 10.1016/s0022-3476(81)80636-1. [DOI] [PubMed] [Google Scholar]
  13. Parmley R. T., Crist W. M., Ragab A. H., Boxer L. A., Malluh A., Lui V. K., Darby C. P. Congenital dysgranulopoietic neutropenia: clinical, serologic, ultrastructural, and in vitro proliferative characteristics. Blood. 1980 Sep;56(3):465–475. [PubMed] [Google Scholar]
  14. Parmley R. T., Tzeng D. Y., Baehner R. L., Boxer L. A. Abnormal distribution of complex carbohydrates in neutrophils of a patient with lactoferrin deficiency. Blood. 1983 Sep;62(3):538–548. [PubMed] [Google Scholar]
  15. Scott R. E., Dale D. C., Rosenthal A. S., Wolff S. M. Cyclic neutropenia in grey collie dogs. Ultrastructural evidence for abnormal neutrophil granulopoiesis. Lab Invest. 1973 Apr;28(4):514–525. [PubMed] [Google Scholar]
  16. 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]
  17. Wright D. G., Dale D. C., Fauci A. S., Wolff S. M. Human cyclic neutropenia: clinical review and long-term follow-up of patients. Medicine (Baltimore) 1981 Jan;60(1):1–13. doi: 10.1097/00005792-198101000-00001. [DOI] [PubMed] [Google Scholar]
  18. Yang T. J., Jones J. B., Jones E. S., Lange R. D. Serum colony-stimulating activity of dogs with cyclic neutropenia. Blood. 1974 Jul;44(1):41–48. [PubMed] [Google Scholar]
  19. Zucker-Franklin D., L'Esperance P., Good R. A. Congenital neutropenia: an intrinsic cell defect demonstrated by electron microscopy of soft agar colonies. Blood. 1977 Mar;49(3):425–436. [PubMed] [Google Scholar]

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