A glycosylphosphatidylinositol-anchored cytokine can function as an artificial cellular adhesin.
A novel strategy for altering the adhesive properties of cells has been developed which is based upon the use of artificial adhesins. Specifically, a glycosylphosphatidylinositol (GPI)-modified variant of the cytokine macrophage colony stimulating factor (M-CSF), designated M-CSF.GPI, was expressed on the surface of human bone marrow stromal cells. A chimeric M-CSF:decay-accelerating factor expression construct was used for M-CSF.GPI expression. Cell:cell binding assays established that this artificially membrane-tethered cytokine functions as a potent cellular adhesin, allowing for enhanced binding to M-CSF receptor-expressing cellular transfectants. Antibody blocking analyses confirmed the M-CSF:M-CSF receptor dependence of the enhanced intercellular binding. This capacity to direct the cellular interactive repertoire of selected cells can in principle be applied to other cell types and other molecular pairs to be used in cell-based therapies.
Weber
M C
MC
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.
Groger
R K
RK
Tykocinski
M L
ML
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D017261:Glycosylphosphatidylinositols; D006801:Humans; D066298:In Vitro Techniques; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry; D014162:Transfection; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D017261:Glycosylphosphatidylinositols; D011956:Receptors, Cell Surface; D016173:Macrophage Colony-Stimulating Factor