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Parasinusoidal location of megakaryocytes in marrow: a determinant of platelet release
Abstract:
Megakaryocytopoiesis occurs in the hematopoietic (extravascular) compartment of marrow. Thus, platelets must traverse the wall of the vascular sinuses of marrow to enter the circulation. We have examined mouse and rat marrow, fixed by rapid immersion so as to maintain anatomical relationships as close to the natural state as possible. Quantitative transmission electron microscopy (TEM) of random transections of femurs established that megakaryocytes reside less than 1 mu from a marrow sinus wall with a probability unlikely to be the result of chance (P less than 0.001). An intimate relationship exists between the megakaryocyte periphery and the abluminal surface of the endothelial lining cell. At the time of platelet release megakaryocyte cytoplasm invaginates and penetrates the endothelial lining cell. The penetrating cytoplasm is detached and enters the marrow circulation. From their dimensions in comparison to circulating platelets, the released cytoplasm represents a packet of platelets that undergoes further fragmentation in the circulation. The parasinusoidal location of megakaryocytes and the process of sinus-wall penetration and platelet delivery was observed by TEM and scanning electron microscopy. These studies provided quantitative support for a specific anatomical arrangement of megakaryocytes in marrow. Moreover, the process of platelet release appears to be a physiological form of metastasis with invasion of vascular walls and vascular spread of cells, that are in this case amitotic.
Insights
Platelets are released from megakaryocytes by penetrating marrow sinus walls. This process, observed in mouse and rat marrow, involves cytoplasm packets detaching and entering circulation for further fragmentation.
Area of Science:
- Hematology
- Cell Biology
- Anatomy
Background:
- Megakaryocytopoiesis, the process of platelet production, occurs in the extravascular space of bone marrow.
- Platelets must exit the extravascular compartment by traversing the walls of vascular sinuses to enter circulation.
Purpose of the Study:
- To investigate the anatomical relationship between megakaryocytes and bone marrow sinus walls.
- To elucidate the mechanism of platelet release from megakaryocytes into circulation.
Main Methods:
- Quantitative transmission electron microscopy (TEM) of mouse and rat femurs.
- Scanning electron microscopy (SEM) was used to visualize the process.
- Rapid immersion fixation preserved natural anatomical relationships.
Main Results:
- Megakaryocytes are located in close proximity (<1 µm) to marrow sinus walls.
- Megakaryocyte cytoplasm invaginates and penetrates endothelial lining cells during platelet release.
- Released cytoplasm packets, containing precursors to platelets, enter the marrow circulation and fragment further.
Conclusions:
- Megakaryocytes exhibit a specific anatomical arrangement in bone marrow, positioned close to vascular sinuses.
- Platelet release is a physiological process involving invasion of vascular walls, akin to metastasis.
- This mechanism facilitates the entry of platelets into circulation for subsequent fragmentation.