ABSTRACT
We have used ultrathin cryosectioning and immunogold cytochemistry to study the position of alpha-granules in the endocytic and biosynthetic pathways in megakaryocytes and platelets. Morphologically, we distinguished three types of granules; so-called multivesicular bodies type I (MVB I) with internal vesicles only, granules with internal vesicles and an electron dense matrix (MVB II), and the alpha-granules with mainly a dense content and often internal membrane vesicles at their periphery. The MVBs were prominent in cultured megakaryocytes and the megakaryoblastic cell line CHRF-288, but were less numerous in bone marrow megakaryocytes and platelets, whereas alpha-granules were most prominent in mature bone marrow megakaryocytes and in platelets. The internalization kinetics of bovine serum albumin-gold particles and of fibrinogen positioned the MVB subtypes and alpha-granules sequentially in the endocytic pathway. MVBs contained the secretory proteins von Willebrand factor (vWF) and beta-thromboglobulin (beta-TG), the platelet-specific membrane protein P-selectin, and the lysosomal membrane protein CD63. Within the MVBs, endocytosed fibrinogen and endogenous beta-TG were restricted to the matrix, while vWF was predominantly associated with internal vesicles. CD63 was also observed in association with internal membrane vesicles in the alpha-granules. These observations, and the gradual morphologic transition from granules containing vesicles to granules containing predominantly dense material, suggest that MVBs represent a developmental stage in alpha-granule maturation.
Subject(s)
Blood Platelets/ultrastructure , Cytoplasmic Granules/ultrastructure , Endocytosis , Animals , Blood Platelets/metabolism , Cattle , Cells, Cultured , Cytoplasmic Granules/metabolism , Humans , Immunohistochemistry , Megakaryocytes/metabolism , Megakaryocytes/ultrastructure , Microscopy, Electron , Serum Albumin, Bovine/metabolismABSTRACT
Mastocytosis is an uncommon disease characterized by a proliferation of tissue mast cells involving various organs, particularly the bone marrow. Though rare, the association of mastocytosis and haematological malignancies is well established. However, the frequency of mastocytosis reported in patients with essential thrombocythaemia is relatively low. We report five cases of such an association. Our five patients were undergoing evaluation for thrombocyte when the bone marrow biopsy revealed the presence of mastocytosis. The pathogenetic significance of this association is poorly understood. The different hypotheses are discussed.
