Decreased stability of erythroblastic islands in integrin β3-deficient mice

Authors

  • Zhenghui Wang,

    1. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zürich and Zürich Center for Integrative Human Physiology (ZIHP), Zürich, Switzerland
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  • Olga Vogel,

    1. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zürich and Zürich Center for Integrative Human Physiology (ZIHP), Zürich, Switzerland
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  • Gisela Kuhn,

    1. Institute for Biomechanics, Swiss Federal Institute of Technology, Zürich, Switzerland
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  • Max Gassmann,

    1. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zürich and Zürich Center for Integrative Human Physiology (ZIHP), Zürich, Switzerland
    2. Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru
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  • Johannes Vogel

    Corresponding author
    • Institute of Veterinary Physiology, Vetsuisse Faculty University of Zürich and Zürich Center for Integrative Human Physiology (ZIHP), Zürich, Switzerland
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Correspondence

Johannes Vogel, Institute of Veterinary Physiology, Vetsuisse Faculty University of Zürich, Winterthurerstr, 260, CH-8057 Zürich, Switzerland.

Tel: +41 44 6358806

Fax: +41 44 6358932

E-mail: jvogel@vetphys.uzh.ch

Abstract

Erythroblasts proliferate and differentiate in hematopoietic organs within erythroblastic islands (EI) composed of erythropoietic progenitor cells attached to a central macrophage. This cellular interaction crucially involves the erythroid intercellular adhesion molecule-4 (ICAM-4) and αv integrin. Because integrins are biologically active as α/β heterodimers, we asked whether β3 could be a heterodimerization partner of αv integrin in EIs. To this end we compared stress erythropoiesis driven by two different mechanisms, namely that of integrin β3-deficient (β3−/−) mice that exhibit impaired hemostasis due to platelet dysfunction with that of systemically erythropoietin-overexpressing (tg6) mice. While compared to the respective wild type (wt) controls β3−/− mice had much less erythropoietic stimulation than tg6 mice β3−/− blood contained more erythrocytes of a lower maturity stage. Unexpectedly, membranes of peripheral erythrocytes from β3−/− mice (but not those from either wt control or from tg6 mice) contained calnexin, a chaperone that is normally completely lost during terminal differentiation of reticulocytes prior to their release into the circulation. In contrast to erythropoietin-overexpressing mice, the erythropoietic subpopulations representing orthochromatic erythroblasts and premature reticulocytes as well as the number of cells per EI were reduced in β3−/− bone marrow. In conclusion, absence of integrin β3 impairs adhesion of the latest erythroid developmental stage to the central macrophage of EIs resulting in preterm release of abnormally immature erythrocytes into the circulation.

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