title: Induction of multinucleated giant cell formation from human blood-derived monocytes by phorbol myristate acetate in in vitro culture.
abstract: Multinucleated giant cells (MGC) of mononuclear phagocyte origin occur in different tissues in various inflammatory states and pathological conditions. Although MGC are believed to be derived from monocyte-derived macrophages by fusion, their mechanism of formation is not known. In this study, we investigated the role of PMA, a protein kinase C activator, in the induction and formation of MGC from blood monocyte-derived macrophages in in vitro culture. The addition of PMA (1 x 10(-9) to 8 x 10(-8) M) to 3-wk-old cultures of blood-derived monocytes induces cell fusion with a 30% to 80% fusion rate. Moreover, IFN-gamma-treated blood-derived monocyte cultures showed an additional enhancement of fusion rate with the addition of PMA. 1(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, a protein kinase inhibitor, inhibited the formation of macrophage-derived giant cells when added before phorbol ester and IFN-gamma. These findings suggest that protein kinase C may play an important role in the formation of macrophage-derived MGC.
authors.affiliation: Division of Allergy, Immunology and Bone Marrow Transplantation, Children's Hospital, Philadelphia, PA 19104.
authors.forename: N F
authors.initials: NF
authors.lastname: Hassan
authors.forename: N
authors.initials: N
authors.lastname: Kamani
authors.forename: M M
authors.initials: MM
authors.lastname: Meszaros
authors.forename: S D
authors.initials: SD
authors.lastname: Douglas
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002459:Cell Fusion / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D010879:Piperazines; D011994:Recombinant Proteins; D007371:Interferon-gamma; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate