Interleukin-3 and Flt3-ligand induce adhesion of Baf3/Flt3 precursor B-lymphoid cells to fibronectin via activation of VLA-4 and VLA-5. 1998

H Shibayama, and N Anzai, and A Ritchie, and S Zhang, and C Mantel, and H E Broxmeyer
Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis 46202, USA.

Adhesion of hematopoietic cells to extracellular matrix components is important for blood cell development. However, little is known regarding the potential influence of IL-3 on this process for precursor B cells and Flt3-ligand has not yet been implicated in induction of adhesion of any blood cell types to extracellular matrix components. Therefore, we examined the characteristics of cytokine-induced cell adhesion to fibronectin (FN), using as a model the murine precursor B cell line, Baf3, a factor-dependent cell line requiring IL-3 for both growth and survival. Since factor-dependent hematopoietic cell lines expressing Flt3 receptor are extremely rare, we also studied Baf3/Flt3, a subline of Baf3 transduced with the Flt3 receptor gene. IL-3 induced adhesion of Baf3 and Baf3/Flt3 cells to FN, while Flt3-ligand induced adhesion of Baf3/Flt3 cells only. Whereas both Baf3 and Baf3/Flt3 cells expressed VLA-4 and -5 integrins as FN receptors, expression levels of VLA-4 and -5 were not affected by IL-3 or Flt3-ligand treatment. However, blocking experiments using anti-integrin antibodies showed that cytokine-induced adhesion of cells depended on both VLA-4 and -5 suggesting that IL-3 and Flt3-ligand activated these integrins. PI-3 kinase inhibitor wortmannin, PKC inhibitor H-7, or PKA inhibitor HA1004 did not suppress adhesion induced by IL-3 or Flt3-ligand; in contrast, PLC inhibitor U-73122 did suppress adhesion, suggesting the possibility that PLC, but not PI-3 kinase, PKC, or PKA, may be involved in this process. Since it is known that IL-3 and Flt3-ligand receptors are expressed on precursor B cells, and these receptors are downregulated during B cell maturation of primary cells, the induction of precursor B cell adhesion to FN by IL-3 and Flt3-ligand may contribute a mechanism by which precursor B cells adhere to bone marrow stroma, thereby influencing their development.

UI MeSH Term Description Entries
D007377 Interleukin-3 A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Burst-Promoting Factor, Erythrocyte,Colony-Stimulating Factor 2 Alpha,Colony-Stimulating Factor, Mast-Cell,Colony-Stimulating Factor, Multipotential,Erythrocyte Burst-Promoting Factor,IL-3,Mast-Cell Colony-Stimulating Factor,Multipotential Colony-Stimulating Factor,P-Cell Stimulating Factor,Eosinophil-Mast Cell Growth-Factor,Hematopoietin-2,Burst Promoting Factor, Erythrocyte,Colony Stimulating Factor, Mast Cell,Colony Stimulating Factor, Multipotential,Eosinophil Mast Cell Growth Factor,Erythrocyte Burst Promoting Factor,Hematopoietin 2,Interleukin 3,Multipotential Colony Stimulating Factor,P Cell Stimulating Factor
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D010738 Type C Phospholipases A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS. Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D011760 Pyrrolidinones A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed) Pyrrolidinone,Pyrrolidone,Pyrrolidones
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D004963 Estrenes Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds. 19-Norandrostenes,19 Norandrostenes
D005353 Fibronectins Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. Cold-Insoluble Globulins,LETS Proteins,Fibronectin,Opsonic Glycoprotein,Opsonic alpha(2)SB Glycoprotein,alpha 2-Surface Binding Glycoprotein,Cold Insoluble Globulins,Globulins, Cold-Insoluble,Glycoprotein, Opsonic,Proteins, LETS,alpha 2 Surface Binding Glycoprotein

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