Multivesicular bodies are an intermediate stage in the formation of platelet α-granules

HFG Heijnen, N Debili, W Vainchencker… - Blood, The Journal …, 1998 - ashpublications.org
HFG Heijnen, N Debili, W Vainchencker, J Breton-Gorius, HJ Geuze, JJ Sixma
Blood, The Journal of the American Society of Hematology, 1998ashpublications.org
We have used ultrathin cryosectioning and immunogold cytochemistry to study the position
of α-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 α-granules with mainly a dense content and often internal
membrane vesicles at their periphery. The MVBs were prominent in cultured …
Abstract
We have used ultrathin cryosectioning and immunogold cytochemistry to study the position of α-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 α-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 α-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 α-granules sequentially in the endocytic pathway. MVBs contained the secretory proteins von Willebrand factor (vWF) and β-thromboglobulin (β-TG), the platelet-specific membrane protein P-selectin, and the lysosomal membrane protein CD63. Within the MVBs, endocytosed fibrinogen and endogenous β-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 α-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 α-granule maturation.
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