title: Reinforcement of integrin-mediated T-Lymphocyte adhesion by TNF-induced Inside-out Signaling.
abstract: Integrin-mediated leukocyte adhesion to endothelial cells is a crucial step in immunity against pathogens. Whereas the outside-in signaling pathway in response to the pro-inflammatory cytokine tumour necrosis factor (TNF) has already been studied in detail, little knowledge exists about a supposed TNF-mediated inside-out signaling pathway. In contrast to the outside-in signaling pathway, which relies on the TNF-induced upregulation of surface molecules on endothelium, inside-out signaling should also be present in an endothelium-free environment. Using single-cell force spectroscopy, we show here that stimulating Jurkat cells with TNF significantly reinforces their adhesion to fibronectin in a biomimetic in vitro assay for cell-surface contact times of about 1.5 seconds, whereas for larger contact times the effect disappears. Analysis of single-molecule ruptures further demonstrates that TNF strengthens sub-cellular single rupture events at short cell-surface contact times. Hence, our results provide quantitative evidence for the significant impact of TNF-induced inside-out signaling in the T-lymphocyte initial adhesion machinery.
authors.affiliation: Institute for Materials Science, Biocompatible Nanomaterials, Christian-Albrechts-Universität zu Kiel, Kaiserstr. 2, D-24143 Kiel, Germany.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute for Materials Science, Biocompatible Nanomaterials, Christian-Albrechts-Universität zu Kiel, Kaiserstr. 2, D-24143 Kiel, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Huth
authors.affiliation: Institute of Immunology, Christian-Albrechts-Universität zu Kiel, Michaelisstr. 5, D-24105 Kiel, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Adam
authors.affiliation: Institute for Materials Science, Biocompatible Nanomaterials, Christian-Albrechts-Universität zu Kiel, Kaiserstr. 2, D-24143 Kiel, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Selhuber-Unkel
mesh_terms: D001696:Biomechanical Phenomena; D040761:Biomimetic Materials / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D019169:Jurkat Cells; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects; D013057:Spectrum Analysis; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D020099:Coated Materials, Biocompatible; D005353:Fibronectins; D016023:Integrins; D014409:Tumor Necrosis Factor-alpha