Negative regulation of activated alpha-2 integrins during thrombopoiesis.

Zou Z, Schmaier AA, Cheng L, Mericko P, Dickeson SK, Stricker TP, Santoro SA, Kahn ML
Blood. 2009 113 (25): 6428-39

PMID: 19258597 · DOI:10.1182/blood-2008-08-175356

Circulating platelets exhibit rapid signaling and adhesive responses to collagen that facilitate hemostasis at sites of vessel injury. Because platelets are anuclear, their collagen receptors must be expressed by megakaryocytes, platelet precursors that arise in the collagen-rich environment of the bone marrow. Whether and how megakaryocytes regulate collagen adhesion during their development in the bone marrow are unknown. We find that surface expression of activated, but not wild-type, alpha2 integrins in hematopoietic cells in vivo results in the generation of platelets that lack surface alpha2 receptors. Culture of hematopoietic progenitor cells ex vivo reveals that surface levels of activated, but not wild-type, alpha2 integrin receptors are rapidly down-regulated during cell growth on collagen but reach wild-type levels when cells are grown in the absence of collagen. Progenitor cells that express activated alpha2 integrins are normally distributed in the bone marrow in vivo and exhibit normal migration across a collagen-coated membrane ex vivo. This migration is accompanied by rapid down-regulation of activated surface integrins. These studies identify ligand-dependent removal of activated alpha2 receptors from the cell surface as a mechanism by which integrin function can be negatively regulated in hematopoietic cells during migration between the adhesive environment of the bone marrow and the nonadhesive environment of the circulating blood.

MeSH Terms (25)

Animals Blood Cells Bone Marrow Cells Cell Adhesion Cell Differentiation Cell Line, Tumor Cell Movement Collagen Hematopoietic Stem Cells Hematopoietic Stem Cell Transplantation Integrin alpha2 Integrin beta1 Leukemia, Basophilic, Acute Liver Megakaryocytes Mice Mice, Inbred C57BL Mice, Knockout Platelet Membrane Glycoproteins Point Mutation Protein Binding Radiation Chimera Rats Recombinant Fusion Proteins Thrombopoiesis

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