title: Polymorphonuclear neutrophil and megakaryocyte mutual involvement in myelofibrosis pathogenesis.
abstract: The study presented here, performed on the bone marrow from patients with idiopathic myelofibrosis (MF) and on a murine model of MF, demonstrates a pathological interaction between PMN leukocytes and megakaryocyte (Mk), correlated with MF development. The data obtained revealed abnormal subcellular P-selectin distribution, which appeared to correlate with excessive and pathological emperipolesis of PMN leukocytes within Mk, leading to the destruction of Mk storage organelles and leakage of alpha-granular contents into the bone marrow microenvironment. The prominent role of growth factors, PDGF and TGFbeta, stored in the Mk alpha-granular compartment in the generation of MF has been previously largely documented. Both growth factors are essential for the Mk-dependent fibroblast proliferation. The destructive mutual cellular interaction of Mk and PMN leading to the pathological release of PDGF and TGFbeta within the bone marrow microenvironment may participate, through fibroblast activation, to the generation of MF. Therefore, this study provides insight into the possible pathophysiological mechanisms for the genesis of MF.
authors.affiliation: INSERM U.474, Intitut Cochin de Génétique Moléculaire, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.forename: Arnaud
authors.initials: A
authors.lastname: Drouin
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Massé
authors.forename: Josette
authors.initials: J
authors.lastname: Guichard
authors.forename: Hedia
authors.initials: H
authors.lastname: Shagraoui
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Cramer
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D002450:Cell Communication; D002455:Cell Division; D004195:Disease Models, Animal; D006801:Humans; D008533:Megakaryocytes / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000032:analysis; D055728:Primary Myelofibrosis / Q000209:etiology* / Q000473:pathology; D013926:Thrombopoietin / Q000235:genetics
chemical_list: D019007:P-Selectin; D013926:Thrombopoietin