title: Increased differentiation of dermal mast cells in mice lacking the Mpl gene.
abstract: Thrombopoietin interactions with its receptor, Mpl, play an important role in the regulation of hematopoietic stem/progenitor cell proliferation and differentiation. In this study, we report that the mast cell restricted progenitor cells (MCP) and the mast cell precursors in the bone marrow of wild-type mice express Mpl on their surface. Furthermore, targeted deletion of the Mpl gene in mice decreases the number of MCP while increasing the number of mast cell precursors present in the marrow and spleen. It also increases the number of mast cells present in the dermis, in the peritoneal cavity, and in the gut of the mice. In addition, serosal mast cells from Mpl(null) mice have a distinctive differentiation profile similar to that expressed by wild-type dermal mast cells. These results suggest that not only does ligation of thrombopoietin with the Mpl receptor exert an effect at the mast cell restricted progenitor cell level, but also plays an unexpected yet important role in mast cell maturation.
authors.affiliation: Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ghinassi
authors.forename: Maria
authors.initials: M
authors.lastname: Zingariello
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Martelli
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lorenzini
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Rosa Alba
authors.initials: RA
authors.lastname: Rana
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Giovanni
authors.initials: G
authors.lastname: Migliaccio
authors.forename: John
authors.initials: J
authors.lastname: Mascarenhas
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Migliaccio
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D020405:Dermis / Q000166:cytology* / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009928:Organ Specificity / Q000235:genetics; D010529:Peritoneal Cavity / Q000166:cytology; D053628:Receptors, Thrombopoietin; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013926:Thrombopoietin / Q000235:genetics / Q000378:metabolism
chemical_list: C481270:Mpl protein, mouse; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin