title: Adhesion of activated natural killer cells to tumor necrosis factor-alpha-treated endothelium under physiological flow conditions.
abstract: Adhesion of activated natural killer (A-NK) cells to activated and nonactivated endothelial cells in vitro was studied under dynamic flow conditions. Endothelial cells grown on glass slides were either treated with tumor necrosis factor-alpha (TNF alpha) or medium, then placed into a flow chamber over which suspensions of A-NK cells were passed using a range of defined shear stress levels. Significant numbers of binding cells could be consistently observed at shear stress levels less than 3 dyn/cm2 on TNF alpha-activated endothelium or at 0.59 dyn/cm2 on nonactivated endothelium. Stable adhesion occurred rapidly following the initial interaction of the following cells with the endothelium in the absence of detectable rolling. Pretreatment of the A-NK cells with monoclonal antibodies directed against CD18 (LFA-1) or CD49d (VLA-4) resulted in a significant reduction in the number of binding cells. Simultaneous treatment with both monoclonal antibodies eliminated all A-NK adhesion occurring over 0.5 dyn/cm2. Pretreatment of the endothelial cells with antibodies against E- or P-selectin resulted in a small but significant reduction in binding only at 0.5 dyn/cm2. The binding efficiency of the A-NK cells was similar to that previously observed for T lymphocytes under the same conditions. Once bound, approximately half of the adherent cells could resist detachment when exposed to wall shear stresses over 12 dyn/cm2. These findings indicate that A-NK cell adhesion to activated endothelium can occur under shear stress conditions which are representative of postcapillary venules and that this binding is mediated principally by both CD18 and CD49d. A-NK cell adhesion also occurs to nonactivated endothelium but only at wall shear stress levels less than 1 dyn/cm2.
authors.affiliation: Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Melder
authors.forename: G C
authors.initials: GC
authors.lastname: Koenig
authors.forename: L L
authors.initials: LL
authors.lastname: Munn
authors.forename: R K
authors.initials: RK
authors.lastname: Jain
mesh_terms: D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D012212:Rheology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha