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Decreased stability of erythroblastic islands in integrin β3-deficient mice


Wang, Zhenghui; Vogel, Olga; Kuhn, Gisela; Gassmann, Max; Vogel, Johannes (2013). Decreased stability of erythroblastic islands in integrin β3-deficient mice. Physiological Reports, 1(2):online.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:24 Jul 2013 09:04
Last Modified:05 Apr 2016 16:52
Publisher:Wiley Open Access
ISSN:2051-817X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/phy2.18
PubMed ID:24303107
Permanent URL: https://doi.org/10.5167/uzh-79490

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