title: Decreased stability of erythroblastic islands in integrin β3-deficient mice.
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.
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty University of Zürich and Zürich Center for Integrative Human Physiology (ZIHP) Zürich, Switzerland.
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Wang
authors.forename: Olga
authors.initials: O
authors.lastname: Vogel
authors.forename: Gisela
authors.initials: G
authors.lastname: Kuhn
authors.forename: Max
authors.initials: M
authors.lastname: Gassmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogel
keywords: Bone marrow niche; calnexin; chaperone; erythroblast differentiation; erythroblastic island; integrins; stress erythropoiesis