From megakaryocytes to platelets: platelet morphogenesis takes place in the bloodstream

Abstract

We studied megakaryocyte processes formed in rat bone marrow and spleen, using both the transmission and scanning electron microscopes. Some processes were bulky, others slender and beaded. The bulky megakaryocyte processes developed a specialized arrangement of organelles at the site at which they entered the lumen: filaments present around the outside of the process seemed to support a central cylinder in which organelles flowed along microtubules. Megakaryocyte processes were present in platelet‐rich plasma from both human and rat blood. When followed in living preparations, bulky processes developed pointed tips, elongated, and became slender and beaded. Fusiform proplatelets also were present in the platelet rich plasma, with pointed tips at both ends of what appeared to be single “beads”; we assume that the long, beaded megakaryocyte processes would have fragmented were we to have had proper culture conditions. The straight, shorter fusiform proplatelets in living preparations underwent characteristic curving and bending motions, eventually forming disk‐shaped cells which sometimes had appendages. This behaviour suggests that the entire process of platelet morphogenesis takes place in plasma: megakaryocyte processes first elongate, then bead and fragment, and then curve and fuse to form disk‐shaped platelets. This interpretation is strengthened by finding in freshly isolated plasma many of the shapes seen in the transformations studied in living cell preparations. The megakaryocyte processes and the proplatelets seemed to appear in plasma with a periodicity related to light and dark cycles – that is, with a circadian rhythm. In particular, megakaryocyte processes appear in human blood within a few hours after sunrise; we argue that this might be related to similar peak periods for heart attacks.

Microtubule and cortical forces determine platelet size during vascular platelet production

“…Large PLTs often occur concomitantly with periods of PLT depletion in humans 8 and various forms of MK processes, and proPLTs are present in cytospin preparations of human PRP 9 . Nevertheless, because barbell-proPLTs are not detected in human blood smears, it is unclear whether these circulate in blood, and their role in thrombocytopenia has not been studied.…”

Gegenwärtige Modelle der Thrombozytopoese

“…Weil die Thrombozytenkonzentration nach der pulmonalen Passage ansteigt, wird das Kapillarbett der Lunge auch als Gewebefilter bezeichnet, wobei die zugrunde liegende Physiologie rätsel-haft bleibt [15,26]. Neben einzelnen MKs können auch Plättchenvorläufer im peripheren Blut nachgewiesen werden, was die These unterstützt, dass zumindest nicht alle Thrombozyten bereits als reife Blutbestandteile unmittelbar im Knochenmark freigesetzt werden [4]. In einer aktuellen Studie wurde gezeigt, dass auch reife Thrombozyten in der Peripherie weiter fragmentiert werden können [31], wobei dieser Mechanismus sicherlich nicht maßgeblich zur gesamten Thromboztenproduktion beitragen wird.…”

De macro à micro : l’histoire de la plaquette

“…La formation directe de plaquettes, sans passer par une étape intermédiaire de proplaquettes, semble plus rare, mais elle est techniquement difficile à visualiser. Ces résultats confirment ceux de O. Behnke qui avait identifié dans le sang circulant chez l'homme, la présence de proplaquettes capables de se fragmenter in vitro en plaquettes [12]. T. Junt et al ont également observé la migration d'un mégacaryocyte qui, momentanément, obstrue la circulation dans les sinusoï-des.…”