Adhesion of mature polyploid megakaryocytes to fibronectin is mediated by beta 1 integrins and leads to cell damage.
Human CD34+ bone marrow cells were committed to the megakaryocytic lineage in serum-free liquid cultures by the following cytokines: thrombopoietin, erythropoietin, and IL-6. Megakaryocyte maturation has been described as being regulated by the extracellular matrix. These cells express receptors for laminin, collagen, and vitronectin, but they selectively adhere to and spread on fibronectin, a major component of the bone marrow environment. Function-perturbing antibodies against beta 1 integrins totally abolished the adhesion of megakaryocytes on fibronectin, whereas antibodies to beta 3 did not, suggesting that beta 1 integrins were responsible for the adhesive phenotype of these polyploid cells. beta 1-positive clusters were visualized in close contact with the extremities of stress fibers at the cell surface. In the course of cell spreading, we observed morphological modifications such as the disorganization of the compact nuclei structure and the appearance of holes in the cytoplasm leading to the release of alpha IIb beta 3-positive cellular fragments. This process appeared to be a specific feature of megakaryocytes and is correlated neither to apoptosis nor to integrin signaling.
Institut National de la Santé et de la Recherche Médicale Unité 318, Département de Biologie Moléculaire et Structurale, Centre d'études Nucléaires, Grenoble, France.
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Berthier
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Jacquier-Sarlin
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Schweitzer
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Block
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Molla
D008841:Actin Cytoskeleton; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001769:Blood; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D002467:Cell Nucleus; D002478:Cells, Cultured; D006224:Cricetinae; D003572:Cytochalasins / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000032:analysis; D008533:Megakaryocytes / Q000166:cytology* / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D011107:Polylysine; D011123:Polyploidy; D017469:Receptors, Fibronectin / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013926:Thrombopoietin / Q000494:pharmacology
D018952:Antigens, CD34; D003572:Cytochalasins; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017469:Receptors, Fibronectin; D011994:Recombinant Proteins; D011107:Polylysine; C047981:arginyl-glycyl-aspartic acid; D013926:Thrombopoietin; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline