Cyclic ultrastructural abnormalities in human cyclic neutropenia.
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.
D000293:Adolescent; D000380:Agranulocytosis / Q000473:pathology*; D001343:Autophagy; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure; D006801:Humans; D007958:Leukocyte Count; D008264:Macrophages / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009503:Neutropenia / Q000235:genetics / Q000473:pathology*; D009504:Neutrophils / Q000648:ultrastructure*; D010507:Periodicity; D013194:Staining and Labeling; D014617:Vacuoles / Q000648:ultrastructure