Of mice and men: Comparison of the ultrastructure of megakaryocytes and platelets

Objective. Mice provide an excellent model for studying platelet and megaka ryocyte (Mk) biology in vivo. Given the increasing use of transgenic and kn ockout mice, it is important that any similarities and differences between murine and human platelet/Mk biology be well defined. Therefore the objecti ve of this study was to compare and contrast in detail any significant morp hological differences between Mks, platelets, and mechanisms of thrombopoie sis in humans and mice. Methods. The distinctive structural and ultrastructural features of murine and human platelets and Mks are reviewed. Several platelet and Mk glycoprot eins were also localized in murine cells by immunoelectron microscopy using polyclonal antibodies directed against human platelet proteins and compare d to existing human data. Finally, the ultrastructure of maturing murine an d human Mks in culture and bone marrow were examined in detail to facilitat e a comparison of either in vivo or in vitro platelet production. Results. Human and murine platelets exhibit significant but well-establishe d morphological differences. Murine platelets are smaller and more numerous and display much greater granule heterogeneity than their human counterpar ts. Immunoelectron microscopy also demonstrated that murine platelet alpha -gramiles, are highly compartmentalized. In fact, they are remarkably simil ar to human alpha -granules, with asymmetrical distribution of von Willebra nd factor (vWF), and labeling of alpha (IIb)beta (3) and P-selectin (CD62P) in the granule limiting membrane. In vivo, murine but not human Mks are al so consistently localized within the, spleen. Subcellular events accompanyi ng platelet formation and release by murine Mks are presented for the first time, and compared to human. Consistent differences were found in the path way of redistribution of demarcation membranes preceding platelet formation , which may be important for the clarification of the mechanism of platelet release. Conclusion. Human and murine platelets and Mks display several characterist ic ultrastructural differences (size, number, histological distribution, pl atelet shedding) which have been emphasized and analyzed in this report. Ne vertheless, since there are also many close similarities (organelle and gly coprotein subcellular distribution) mice offer an excellent in vivo model t o study various aspects of human Mk and platelet biology. (C) 2001 Internat ional Society for Experimental Hematology. Published by Elsevier Science In c.