title: Tumour necrosis factor triggers granulocytes to internalize complement-coated virus particles.
abstract: Monocytes produced tumour necrosis factor-alpha (TNF-alpha) upon interaction with infective herpes simplex virus (HSV). Therefore, TNF-alpha and its action were examined in the regulation of anti-viral functions of human polymorphonuclear leucocytes (PMN). The uptake of fluorescein-labelled HSV by human PMN was monitored using flow cytometric analysis. As shown in earlier work, complement-coated herpes virions were bound to PMN but were not internalized. However, after priming with recombinant human TNF-alpha, complement-coated virions were taken up by human PMN. This complement receptor-mediated internalization is a new observation, both because it affects PMN and it is induced by a recombinant cytokine. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), another priming factor of PMN, was unable to induce this phenomenon. By contrast, other parameters of PMN anti-viral defence were enhanced to the same extent by both TNF-alpha and GM-CSF. PMN primed by either TNF-alpha or GM-CSF showed both an enhanced respiratory burst and an increased membrane potential depolarization when triggered by immune complexes containing HSV, antibody and complement. Both primers rendered an enhanced uptake of HSV in the presence of specific antibody and in the presence of both antibody and complement, but they caused no effect on the rate or quantity of processing of phagocytosed HSV particles by PMN. We propose that TNF-alpha and GM-CSF act as effective modulators of PMH to enhance virus removal, especially in inflammatory sites. We tentatively conclude that TNF-alpha together with PMN and complement represent a novel non-specific defence mechanism against HSV.
authors.affiliation: Eijkman-Winkler Laboratory of Medical Microbiology, Utrecht University, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: van Strijp
authors.forename: M E
authors.initials: ME
authors.lastname: van der Tol
authors.forename: L A
authors.initials: LA
authors.lastname: Miltenburg
authors.forename: K P
authors.initials: KP
authors.lastname: van Kessel
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
mesh_terms: D003165:Complement System Proteins / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006561:Herpes Simplex / Q000276:immunology; D006801:Humans; D008163:Luminescent Measurements; D008564:Membrane Potentials / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D018139:Simplexvirus; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins