G-CSF induces E-selectin ligand expression on human myeloid cells
| Autor: | Joel A. Spencer, Nilesh M. Dagia, Charles P. Lin, Samah Z. Gadhoum, Christine A Knoblauch, Parisa Zamiri, Robert Sackstein |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Glycan
beta-Galactoside alpha-2 3-Sialyltransferase Myeloid Endothelium Lewis X Antigen Bone Marrow Cells Inflammation CHO Cells General Biochemistry Genetics and Molecular Biology Mice Cricetinae Granulocyte Colony-Stimulating Factor Glycosyltransferase E-selectin medicine Animals Humans Myeloid Cells Cell adhesion biology Tumor Necrosis Factor-alpha General Medicine Fucosyltransferases Sialyltransferases Cell biology Hyaluronan Receptors medicine.anatomical_structure Gene Expression Regulation Biochemistry biology.protein medicine.symptom E-Selectin Intravital microscopy |
| Zdroj: | Nature Medicine. 12:1185-1190 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm1470 |
| Popis: | Clinical use of G-CSF can result in vascular and inflammatory complications. To investigate the molecular basis of these effects, we analyzed the adherence of G-CSF-mobilized human peripheral blood leukocytes (ML) to inflamed (TNF-alpha-stimulated) vascular endothelium. Studies using parallel plate assays under physiologic flow conditions and intravital microscopy in a mouse inflammation model each showed that ML take part in heightened adhesive interactions with endothelium compared to unmobilized (native) blood leukocytes, mediated by markedly increased E-selectin receptor-ligand interactions. Biochemical studies showed that ML express the potent E-selectin ligand HCELL (ref. 8) and another, previously unrecognized approximately 65-kDa E-selectin ligand, and possess enhanced levels of transcripts encoding glycosyltransferases (ST3GalIV, FucT-IV and FucT-VII) conferring glycan modifications associated with E-selectin ligand activity. Enzymatic treatments and physiologic binding assays showed that HCELL and the approximately 65-kDa E-selectin ligand contribute prominently to the observed G-CSF-induced myeloid cell adhesion to inflamed endothelium. Treatment of normal human bone marrow cells with a pharmacokinetically relevant concentration of G-CSF in vitro resulted in increased expression of these two molecules, coincident with increased transcripts encoding pertinent glycosyltransferases and heightened E-selectin binding. These findings provide direct evidence for a role of G-CSF in the induction of E-selectin ligands on myeloid cells, thus providing mechanistic insight into the pathobiology of G-CSF complications. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|