critical for erythroblastic island formation Targeted gene deletion demonstrates that cell adhesion molecule ICAM-4 is

ABSTRACT 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 α V integrins as ICAM-4 counterreceptors. Since macrophages express α 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/α V adhesion produced a 53-57% decrease in reconstituted islands, strongly suggesting that ICAM-4 binding to macrophage α