Holey red cells: a brief note.
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Biomedical subjects
Publications and source records attributed to P A Santillo.
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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.
Figure 16 synthesizes the various aspects of marrow egress. The central anatomical relationship of the hematopoietic compartment to vascular sinus is shown above. The hatched blocks represent the sinus wall, capable of developing narrow migration channels. In the marrow, immature granulocytes alter their biophysical characteristics by developing motility, nuclear and cytoplasmic deformability and surfaces which facilitate egress. Humoral factors contribute to proliferation and maturation. Also, other humoral agents, releasing factors, may act on mature cells, for example, as cytoattractants, and on the sinus wall to reduce its adventitial cover and thereby to enhance egress. In the sinus, flow or discharge of sinus contents may be regulated by humoral agents or neural messages which may affect terminal sphincters or other structures. Although the marrow in situ is a difficult organ to study, future innovations are to be expected and our understanding of the delicate balance between hematopoietic cells, stroma and vasculature will be enhanced. Corrections of inferential errors due in part to the semi-quantitative and qualitative nature of much of our current data should be expected.
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