Fractalkine-upregulated milk-fat globule EGF factor-8 protein in cultured rat microglia.
Fractalkine is the only known member of the CX(3)C-chemokine family, and so is its receptor CX(3)CR1. Fractalkine, typically is expressed by neurons where it is inserted in the plasma membrane ("chemokine on a stalk"). It can, however, be clipped off by a specific enzyme and diffuse into the extracellular space. CX(3)CR1 is primarily expressed by microglia, the phagocytes of the brain. This study was aimed at studying gene expression changes in cultured rat microglia upon fractalkine stimulation using gene chip technology. Six genes turned out to be upregulated, amongst which milk-fat globule EGF factor-8 protein (MFG-E8) was the most surprising, but also the most revealing one. We hypothesize that it serves as a bridging molecule between apoptotic cells (neurons) and microglia. Since the docking to microglia is, in part, mediated by members of the integrin family, six of these molecules have been-post hoc-included in real-time PCR confirmations of chip results. Two of them-integrin alpha(2) and integrin beta(5)-were upregulated as well. These data provide a much closer look into molecular mechanisms involved in apoptosis of neurons and their removal by microglia.
Leonardi-Essmann
Fernando
F
Central Institute for Mental Health, Department of Psychopharmacology, J5, 68159 Mannheim, Germany.
Emig
Michael
M
Kitamura
Yoshihisa
Y
Spanagel
Rainer
R
Gebicke-Haerter
Peter J
PJ
D000818:Animals; D000954:Antigens, Surface; D037281:Calnexin / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000502:physiology*; D020869:Gene Expression Profiling; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D038362:Glycogen Synthase Kinase 3; D006017:Glycolipids / Q000096:biosynthesis* / Q000235:genetics; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D039421:Integrin alpha2 / Q000096:biosynthesis / Q000235:genetics; D066292:Lipid Droplets; D008565:Membrane Proteins / Q000502:physiology*; D017628:Microglia / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008894:Milk Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D038941:Polypyrimidine Tract-Binding Protein; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
D000954:Antigens, Surface; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D006017:Glycolipids; D006023:Glycoproteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D039421:Integrin alpha2; C499941:MFGE8 protein, rat; D008565:Membrane Proteins; D008894:Milk Proteins; D009124:Muscle Proteins; C475523:Ptbp1 protein, rat; D016601:RNA-Binding Proteins; D009418:S100 Proteins; C110367:milk fat globule; D038941:Polypyrimidine Tract-Binding Protein; D037281:Calnexin; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase