title: Alteration in the responsiveness to tumour necrosis factor-alpha is crucial for maximal expression of monocyte chemoattractant protein-1 in human neutrophils.
abstract: We previously reported delayed expression of monocyte chemoattractant protein-1 (MCP-1) in human neutrophils cultured with a cytokine-rich crude supernatant of phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PHA-sup). Tumour necrosis factor-alpha (TNF-alpha) contained in the PHA-sup played a key role in this event, but there appeared to be another factor(s) in the same supernatant that co-operated with TNF-alpha for maximal MCP-1 expression. In the present study, we reduced TNF-alpha concentrations in the PHA-sup to minimal levels using anti-TNF-alpha affinity columns (TNF-depleted-sup) and investigated the co-operation between TNF-alpha and TNF-depleted-sup. Nine hours of preincubation with TNF-depleted-sup altered the responsiveness of neutrophils to TNF-alpha and enabled TNF-alpha to increase the level of MCP-1 expression to a maximal level within 4 hr. The priming effect was not due to the increased expression of cell-surface TNF receptors. However, the activation of primed cells by TNF-alpha was clearly through TNF receptor-p55. Finally, the activity in the TNF-depleted-sup that co-operated with TNF-alpha was eluted at 60 000 MW on high-performance liquid chromatography-gel filtration. Thus, delayed neutrophil expression of MCP-1 is regulated by a cytokine-dependent mechanism that induces neutrophils to enter a 'mature' stage.
authors.affiliation: Laboratory of Molecular Immunoregulation, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yamashiro
authors.forename: H
authors.initials: H
authors.lastname: Kamohara
authors.forename: T
authors.initials: T
authors.lastname: Yoshimura
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation; D006801:Humans; D009504:Neutrophils / Q000276:immunology*; D010835:Phytohemagglutinins / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha