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Blood, 15 September 2006, Vol. 108, No. 6, pp. 2064-2071. Prepublished online as a Blood First Edition Paper on May 11, 2006; DOI 10.1182/blood-2006-03-006759. This Article Full Text (PDF) All Versions of this Article: blood-2006-03-006759v1 108/6/2064    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lee, G. Articles by Chasis, J. A. Search for Related Content PubMed PubMed Citation Articles by Lee, G. Articles by Chasis, J. A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 8, 2006 Accepted April 30, 2006 Targeted gene deletion demonstrates that cell adhesion molecule ICAM-4 is critical for erythroblastic island formation Gloria Lee, Annie Lo, Sarah A Short, Tosti J Mankelow, Frances Spring, Stephen F Parsons, Karina Yazdanbakhsh, Narla Mohandas, David J Anstee, and Joel Anne Chasis* University of California, Lawrence Berkeley National Laboratory, Berkeley, CA, USA The Bristol Institute for Transfusion Sciences, Bristol, UK The New York Blood Center, New York, NY, USA * Corresponding author; email: jachasis{at}lbl.gov. Erythroid progenitors differentiate in erythroblastic islands, bone marrow niches composed of erythroblasts surrounding a central macrophage. Evidence suggests that within islands adhesive interactions regulate erythropoiesis and apoptosis. We are exploring whether erythroid intercellular adhesion molecule-4 (ICAM-4), an immunoglobulin superfamily member, participates in island formation. Earlier, we identified V integrins as ICAM-4 counterreceptors. Since macrophages express V, ICAM-4 potentially mediates island attachments. To test this, we generated ICAM-4 knockout mice and developed quantitative, live cell techniques for harvesting intact islands and for reforming islands in vitro. We observed a 47% decrease in islands reconstituted from ICAM-4 null marrow compared to wild type. We also found a striking decrease in islands formed in vivo in knockout mice. Further, peptides that block ICAM-4/V adhesion produced a 53-57% decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage V functions in island integrity. Importantly, we documented that V integrin is expressed in macrophages isolated from erythroblastic islands. Collectively, these data provide convincing evidence that ICAM-4 is critical in erythroblastic island formation via ICAM-4/V adhesion and also demonstrate that the novel experimental strategies we developed will be valuable in exploring molecular mechanisms of erythroblastic island formation and their functional role in regulating erythropoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ICAM-4 lands on the erythroblast island James Palis Blood 2006 108: 1793-1794. [Full Text] [PDF] This article has been cited by other articles: K. E. McGrath, P. D. Kingsley, A. D. Koniski, R. L. Porter, T. P. Bushnell, and J. Palis Enucleation of primitive erythroid cells generates a transient population of "pyrenocytes" in the mammalian fetus Blood, February 15, 2008; 111(4): 2409 - 2417. [Abstract] [Full Text] [PDF] M. M. Rhodes, P. Kopsombut, M. C. Bondurant, J. O. Price, and M. J. Koury Adherence to macrophages in erythroblastic islands enhances erythroblast proliferation and increases erythrocyte production by a different mechanism than erythropoietin Blood, February 1, 2008; 111(3): 1700 - 1708. [Abstract] [Full Text] [PDF] B. T. Spike, B. C. Dibling, and K. F. Macleod Hypoxic stress underlies defects in erythroblast islands in the Rb-null mouse Blood, September 15, 2007; 110(6): 2173 - 2181. [Abstract] [Full Text] [PDF] X.-S. Liu, X.-H. Li, Y. Wang, R.-Z. Shu, L. Wang, S.-Y. Lu, H. Kong, Y.-E Jin, L.-J. Zhang, J. Fei, et al. Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver Blood, August 1, 2007; 110(3): 870 - 876. [Abstract] [Full Text] [PDF] P. Sathyanarayana, M. P. Menon, O. Bogacheva, O. Bogachev, K. Niss, W. S. Kapelle, E. Houde, J. Fang, and D. M. Wojchowski Erythropoietin modulation of podocalyxin and a proposed erythroblast niche Blood, July 15, 2007; 110(2): 509 - 518. [Abstract] [Full Text] [PDF] B. O. Fabriek, M. M. J. Polfliet, R. P. M. Vloet, R. C. van der Schors, A. J. M. Ligtenberg, L. K. Weaver, C. Geest, K. Matsuno, S. K. Moestrup, C. D. Dijkstra, et al. The macrophage CD163 surface glycoprotein is an erythroblast adhesion receptor Blood, June 15, 2007; 109(12): 5223 - 5229. [Abstract] [Full Text] [PDF] E. Ihanus, L. M. Uotila, A. Toivanen, M. Varis, and C. G. Gahmberg Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4 Blood, January 15, 2007; 109(2): 802 - 810. [Abstract] [Full Text] [PDF]

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