title: Expression and function of Fas and Fas ligand on peripheral blood lymphocytes in normal subjects.
abstract: We investigated the expression and function of Fas and Fas ligand (FasL) on peripheral blood lymphocytes (PBLs). The cells were stimulated with various cytokines or 12-0-tetradecanoyl phorbol 13-acetate (PMA) plus ionomycin. About 30% of unstimulated PBLs expressed Fas, and the expression was augmented by interleukin-1beta (IL-1beta), IL-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or PMA plus ionomycin. Although only minimal FasL expression was detected on unstimulated PBLs, FasL expression was markedly induced by IL-2 or PMA plus ionomycin, suggesting that Fas and FasL were both expressed on IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Although IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs were positive for both Fas and FasL, no significant increase in apoptosis was demonstrated in these activated PBLs. In addition, treatment of PBLs with IL-2 or PMA plus ionomycin did not change anti-Fas-induced apoptosis, although these activated PBLs expressed Fas strongly when compared with unstimulated PBLs. Only IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs killed Fas+ target cells efficiently via the interaction of Fas on target cells with FasL of PBLs. Bcl-2 was constitutively expressed on unstimulated PBLs, but its expression was significantly augmented by IL-2 or PMA plus ionomycin. The expression of Bax was clearly induced only on IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs and that of other Bcl-2 family proteins such as Bcl-x and Bad could not be detected on human PBLs, including IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Our results suggest that PBLs activated by IL-2 or PMA plus ionomycin express both Fas and FasL and that they kill Fas+ target cells by using FasL on the surface. The resistance of these activated PBLs to Fas-mediated apoptosis may be due to the augmented Bcl-2 expression or the presence of Bcl-2:Bax heterodimers on these cells.
authors.affiliation: The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki City, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawakami
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: N
authors.initials: N
authors.lastname: Matsuoka
authors.forename: M
authors.initials: M
authors.lastname: Tsuboi
authors.forename: T
authors.initials: T
authors.lastname: Koji
authors.forename: S
authors.initials: S
authors.lastname: Urayama
authors.forename: T
authors.initials: T
authors.lastname: Nakashima
authors.forename: Y
authors.initials: Y
authors.lastname: Kawabe
authors.forename: S
authors.initials: S
authors.lastname: Nagataki
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate