Mammalian reticulocytes lose adhesion to fibronectin during maturation to erythrocytes.

Abstract

We describe three situations in which a large fraction of circulating red blood cells attach tightly and specifically to fibronectin: (0) rabbits made anemic by repeated bleeding, (ii) patients with hemolytic anemia and functional asplenia and splenectomized normal humans, and (iii) splenectomized mice. Upon induction of anemia in rabbits, the proportion of circulating red blood cells capable of specifically attaching to fibronectin-coated plastic increased in parallel with the number of reticulocytes. Fibronectin-adherent red cells were barely detectable when the rabbit had recovered from the anemia. Attachment of reticulocytes to fibronectin was specific; cells did not attach to dishes coated with albumin, laminin, or collagen. None of these proteins promoted the attachment of normal erythrocytes. About 75% of the erythrocytes from splenectomized mice (but not control mice) also attached specifically to fibronectin 40 days after surgery. The effect of splenectomy was incomplete and transient; adherent cells were not detectable 8 weeks after splenectomy. As judged by labeling studies with [35S]methionine, newly emergent reticulocytes preferentially attached to fibronectin. We suggest that about half of the reticulocytes in erythropoietically unstressed mice lose their ability to attach to fibronectin, possibly due to loss of fibronectin-adhesive components, during passage through the spleen. The others lose their ability to interact with fibronectin before release, in the bone marrow, or in some extrasplenic site.Erythrocyte production in adult mammals begins in the bone marrow; nucleated erythroid stem cells undergo proliferation and terminal differentiation into nonnucleated reticulocytes, the immediate precursor of mature erythrocytes. Before the final stages of maturation, reticulocytes are released from the bone marrow into the circulation. Reticulocyte maturation is completed within 1-3 days; during this period remnants of mitochondria, Golgi complex, and polyribosomes are eliminated. Reticulocyte maturation also involves the remodeling of the plasma membrane, resulting in loss of the ability to exhibit endocytosis (1-3).Undifferentiated murine erythroleukemia (MEL) cells growing in culture adhere tightly to fibronectin, and erythroid differentiation is accompanied by the loss of adhesion fibronectin (4). Fibronectin is a glycoprotein associated with extracellular matrices of many tissues; it is tightly bound to the surface of many cells, and is also found in the blood plasma (5, 6). Fibronectin is a major component of the interstitial matrix in the bone marrow (7). We speculated that the bone marrow precursors of erythrocytes interact with fibronectin and that loss of fibronectin adhesion is associated with release of the cell into the circulation (4). But the function of such interactions during erythroid differentiation remains to be investigated.We show here that human, rabbit, and mouse reticulocytes specifically attach to fibronectin and that the remodeling of the reticulocyte plasma membran...

Dose-related Differences in the Pharmacodynamic and Toxicologic Response to a Novel Hyperglycosylated Analog of Recombinant Human Erythropoietin in Sprague-Dawley Rats with Similarly High Hematocrit

“…Overall, newly released ''stress'' reticulocytes are more prothrombotic than reticulocytes produced during basal erythropoiesis. They are generally larger, less deformable, and more adhesive in circulation (Chasis et al 1989;Waugh et al 1997;Patel et al 1985). Increasingly immature subpopulations of stress reticulocytes display a more severe phenotype associated with these same attributes and are also more fragile in circulation (Wiczling and Krzyzanski 2008;Wiczling, Ait-Oudhia, and Krzyzanski 2009).…”

Sickle cell disease and stroke

“…Adhesion molecule receptors are particularly enriched on reticulocytes. 84 We suggest that all of these changes may endanger the already damaged cerebral vascular endothelial cells of SCD patients and provoke a complete occlusion. If these damaging factors were further complicated by an elevated Hct, stroke frequency would be even higher than it is.…”

Cross-talk between α4β1/α5β1 and c-Kit results in opposing effect on growth and survival of hematopoietic cells via the activation of focal adhesion kinase, mitogen-activated protein kinase, and Akt signaling pathways

“…[34][35][36][37][38][39][40] To determine if integrins are important mediators of mitogenesis in erythroid cells, we measured DNA synthesis in G1E-ER2 cells and primary fetal liver-derived EPCs cultured on FN peptides in the presence or absence of SCF. After 48 hours in culture on FN peptides, [ 3 H]-thymidine was added for 6 hours and [ 3 H]-thymidine incorporation was determined.…”

“…37,38 Efficient production of mature cells in vitro requires adhesion to FN in some systems. [39][40][41][42] In addition, treatment of normal mice with anti-␣ 4 ␤ 1 antibody completely blocks erythropoiesis. 32 Some evidence of collaboration between c-Kit and integrins also exists.…”