title: Tumor necrosis factor-α can induce Langhans-type multinucleated giant cell formation derived from myeloid dendritic cells.
abstract: The formation of the rich cellular features of MGCs, where the nuclei are arranged circularly at the periphery of the cell (morphologically epithelioid; Langhans-type), is assumed to be associated with any granulomatous disease. The mechanism by which TNF controls the formation of human MGCs in vitro was investigated, focusing on the effect of the TNF-neutralizing antibody. Peripheral blood monocytes were isolated with mAb-coated immunologic magnetic beads and cultured for 10 days in the presence of 20 ng/mL GM-CSF and 10 ng/mL IL-4. These cells were further incubated in the presence of TNF-α with/without its blockade antibodies for 14 days. Myeloid DCs can be generated from peripheral blood monocytes, and both IL-4 and GM-CSF can provide sufficient stimulus for their differentiation. The formation of MGC can be induced in the presence of TNF-α. This reaction was prohibited by the presence of the TNF-neutralizing antibody but not by the presence of anti-TNF receptor II antibody. The activation of Rho and focal adhesion kinases induced by TNF-α stimulation might be linked to cell assembling and the formation of Langhans-type MGCs. MGCs can produce only small amounts of superoxide anions compared to isolated macrophages such as myeloid DCs.
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. k-yasui@city-hosp.naka.hiroshima.jp
authors.forename: Kozo
authors.initials: K
authors.lastname: Yasui
authors.forename: Masato
authors.initials: M
authors.lastname: Yashiro
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tsuge
authors.forename: Yohichi
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yukie
authors.initials: Y
authors.lastname: Saito
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Nagaoka
authors.forename: Nobuko
authors.initials: N
authors.lastname: Yamashita
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Morishima
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015744:Giant Cells, Langhans / Q000166:cytology / Q000276:immunology*; D006805:Human Experimentation; D006801:Humans; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides