Of mice and men: comparison of the ultrastructure of megakaryocytes and platelets.
OBJECTIVE
Mice provide an excellent model for studying platelet and megakaryocyte (Mk) biology in vivo. Given the increasing use of transgenic and knockout mice, it is important that any similarities and differences between murine and human platelet/Mk biology be well defined. Therefore the objective of this study was to compare and contrast in detail any significant morphological differences between Mks, platelets, and mechanisms of thrombopoiesis in humans and mice.


METHODS
The distinctive structural and ultrastructural features of murine and human platelets and Mks are reviewed. Several platelet and Mk glycoproteins were also localized in murine cells by immunoelectron microscopy using polyclonal antibodies directed against human platelet proteins and compared to existing human data. Finally, the ultrastructure of maturing murine and human Mks in culture and bone marrow were examined in detail to facilitate a comparison of either in vivo or in vitro platelet production.


RESULTS
Human and murine platelets exhibit significant but well-established morphological differences. Murine platelets are smaller and more numerous and display much greater granule heterogeneity than their human counterparts. Immunoelectron microscopy also demonstrated that murine platelet alpha-granules are highly compartmentalized. In fact, they are remarkably similar to human alpha-granules, with asymmetrical distribution of von Willebrand 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 also consistently localized within the spleen. Subcellular events accompanying platelet formation and release by murine Mks are presented for the first time, and compared to human. Consistent differences were found in the pathway of redistribution of demarcation membranes preceding platelet formation, which may be important for the clarification of the mechanism of platelet release.


CONCLUSIONS
Human and murine platelets and Mks display several characteristic ultrastructural differences (size, number, histological distribution, platelet shedding) which have been emphasized and analyzed in this report. Nevertheless, since there are also many close similarities (organelle and glycoprotein subcellular distribution) mice offer an excellent in vivo model to study various aspects of human Mk and platelet biology.
Schmitt
A
A
INSERM U.474, Institut Cochin de Génétique Moléculaire, Hôpital de Port-Royal, 123, Boulevard de Port-Royal, 75014 Paris, France.
Guichard
J
J
Massé
J M
JM
Debili
N
N
Cramer
E M
EM
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000648:ultrastructure*; D001853:Bone Marrow / Q000648:ultrastructure; D002462:Cell Membrane / Q000648:ultrastructure; D048429:Cell Size; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D008533:Megakaryocytes / Q000737:chemistry / Q000648:ultrastructure*; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice / Q000033:anatomy & histology* / Q000097:blood; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D019007:P-Selectin / Q000032:analysis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D014841:von Willebrand Factor / Q000032:analysis
D008562:Membrane Glycoproteins; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014841:von Willebrand Factor