Platelet production in the pulmonary capillary bed: new ultrastructural evidence for an old concept

Abstract

Although there is substantial evidence indicating that platelets are released from megakaryocytes in the capillary bed of the lung, this concept has not been universally accepted because much of the evidence has been indirect. To more definitively substantiate that platelet production takes place in the lungs, megakaryocyte and platelet production was accelerated in mice by phlebotomy or by administration of thrombopoietin, and ultrastructural analysis was performed on lung specimens. Intact megakaryocytes, megakaryocyte fragments with numerous demarcated platelet fields, dissociating intact platelets, and denuded megakaryocyte nuclei were seen in the pulmonary capillaries of mice. In addition, some megakaryocyte nuclei exhibited the morphological counterpart of apoptosis. These observations provide evidence for platelet release in the capillary bed of the lungs during stimulated as well as reactive thrombocytosis without precluding observations that some "proplatelets" form in the sinusoids of the bone marrow before transmigration of intact megakaryocytes into the circulation.

Figure 1.

Representative sections of lung from bled mice, showing large fragments of megakaryocyte cytoplasm (arrows) within capillary lumen. The demarcated platelet fields are clearly seen. Also note that the megakaryocyte fragment in A is considerably larger than the lymphocyte (L) or neutrophil (N) within the same capillary lumen. In B an erythrocyte (RBC) is seen within the same lumen as the megakaryocyte fragment. Original magnifications: A, ×8000; B, ×7500.

Figure 2.

Intact megakaryocyte occupying the lumen of a pulmonary capillary. The specimen was obtained from a thrombopoietin-treated mouse. Original magnification, ×9000.

Figure 3.

Megakaryocyte in the lumen of a pulmonary capillary adjacent to numerous platelets (Plt) likely to leave been released by the cell. RBC, erythrocyte. Original magnification, ×4000.

Figure 4.

Denuded megakaryocyte nuclei seen in the capillaries of lungs obtained from thrombopoietin-treated mice. Note erythrocytes (RBC) within the same lumen. The chromatin distribution in the megakaryocyte nuclei is suggestive of apoptosis. The arrow indicates an “apoptic” body. Original magnification, ×4500; inset, ×3000.