Characterization of the murine macrophage mannose receptor: demonstration that the downregulation of receptor expression mediated by interferon-gamma occurs at the level of transcription
| Autor: | N, Harris, M, Super, M, Rits, G, Chang, R A, Ezekowitz |
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| Rok vydání: | 1992 |
| Předmět: |
Transcription
Genetic Molecular Sequence Data Down-Regulation Gene Expression Receptors Cell Surface Transfection Polymerase Chain Reaction Cell Line Interferon-gamma Mice Animals Humans Lectins C-Type Amino Acid Sequence Receptors Immunologic Cells Cultured Gene Library Binding Sites Membrane Glycoproteins Base Sequence Sequence Homology Amino Acid Macrophages Recombinant Proteins Mannose-Binding Lectins Oligodeoxyribonucleotides Mannose Mannose Receptor |
| Zdroj: | Blood. 80(9) |
| ISSN: | 0006-4971 |
| Popis: | The macrophage mannose receptor (MMR) is a 175-Kd cell-surface transmembrane glycoprotein that is expressed on tissue macrophages where it functions both to mediate the uptake of mannose-rich glycoproteins and as a phagocytic receptor for bacteria, yeasts, and other pathogenic microorganisms. In this report we describe the cloning of the full-length cDNA of the mouse macrophage mannose receptor and we investigate the level at which interferon gamma (IFN-gamma) downregulates mannose receptor expression. The latter is a marker of the functional state of the cell as high levels are expressed on resident and inflammatory macrophages, whereas cells activated by treatment with IFN-gamma have decreased-to-absent cell-surface mannose receptor expression. The murine MMR cDNA contains an open reading frame that predicts a protein of 1,456 amino acids. Transient expression of the protein in heterologous cells shows that this cDNA encodes a functional mannose receptor. The deduced amino acid sequence of this protein has an overall 82% homology with the human mannose receptor and as such, the ectodomain contains an N-terminus that is cysteine-rich followed by a fibronectin type II domain and eight carbohydrate recognition domains (CRDs). The ectodomain is linked to a hydrophobic transmembrane region and a 46-amino acid cytoplasmic tail. All of the eight CRDs are particularly well conserved, especially CRD4, which shows 92% homology with the equivalent region of the human protein. Steady-state levels of murine MMR mRNA were measured in the macrophage cell line J774E, which is known to express the protein at the cell surface. These levels were decreased by a 4- to 8-hour incubation with IFN-gamma, but were almost abolished by overnight treatment with this cytokine. Nuclear run-on experiments showed that IFN-gamma inhibits MMR gene transcription. Therefore, the regulation of mannose receptor expression by IFN-gamma provides a novel system in which to study the mechanisms by which this cytokine represses gene expression. |
| Databáze: | OpenAIRE |
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