Megakaryocytopoiesis and granulopoiesis in W/Wv mice: comparisons between bone marrow and spleen.
To determine how megakaryocyte progenitor cells (CFU-M) of W/Wv mice are affected by the hematopoietic stem cell abnormality, megakaryocytopoiesis was studied in the spleen and marrow of these genetically anemic W/Wv mice. CFU-M were assayed in the soft gel colony-forming system. Megakaryocyte colony size was determined by counting the number of megakaryocytes per colony, and megakaryocyte diameter was determined on acetylcholinesterase-stained cytocentrifuged cell preparations with use of an eyepiece micrometer. In spite of normal blood platelet levels, megakaryocyte level was reduced in the spleen and humerus to about 60% that of +/+ littermates. Megakaryocyte diameters were increased in W/Wv mice. CFU-M in W/Wv mice were reduced to 40% the number seen in the spleen of +/+ mice and to 62% in the humerus. In cell cycle studies, significantly fewer marrow CFU-M were in DNA synthesis in W/Wv mice compared with +/+ animals, but similar numbers of cells were in cycle in the spleen for both genotypes. No difference was observed between W/Wv and +/+ CFU-M in their requirement for exogenous colony-stimulating activity or in the distribution of colony sizes. However, CFU-M-derived colonies cloned from adherent cell-depleted marrow cells were significantly smaller compared with those cultured from unfractionated marrow cells. Results for granulocytes and granulocyte-macrophage progenitor cells (CFU-GM) were similar to those obtained for the megakaryocyte series, indicating that the abnormalities are present in different cell lineages. These results suggest that the macromegakaryocytosis of W/Wv mice appears to be a compensation for the megakaryocytopenia. Cells in the progenitor cell compartment appeared not to be involved in this compensation. Furthermore, adherent cells appear to elaborate a factor regulating megakaryocyte development. These findings are compatible with two-level regulation of megakaryocyte formation and a complex mechanism of blood platelet level regulation.
Petursson
S R
SR
Department of Medicine, University of Pittsburgh School of Medicine, PA 15261.
Chervenick
P A
PA
D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002478:Cells, Cultured; D006098:Granulocytes / Q000166:cytology; D006400:Hematocrit; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D010976:Platelet Count; D013154:Spleen / Q000166:cytology*