Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide.
Dendritic cells (DC) are potent antigen-presenting cells that are important for the priming of antitumor cytotoxic T cells. Recent reports suggest that DC may also have direct cytotoxic effector functions against selected tumor-cell lines by mechanisms that are dependent on dendritic cell-tumor cell contact in vitro. The authors report that ex vivo-generated murine DC induce the apoptosis of a panel of syngeneic and allogeneic murine tumors. Apoptosis of the MCA205 fibrosarcoma tumor-cell line by C57BL/6-derived DC was not mediated by Fas/FasL interactions and, in contrast to other studies, DC-tumor cell contact was not required to effect tumor-cell killing by DC. Therefore, the authors postulated that tumor-cell killing was mediated by an apoptotic factor that was secreted by DC. Even though DC did not secrete such apoptotic cytokines as interferon-alpha or tumor necrosis factor-alpha, they did secrete nitric oxide, and tumor apoptosis was partially abrogated by the nitric oxide synthase antagonist NG-monomethyl-L-arginine. Therefore, the authors' data demonstrate a novel mechanism for DC-induced tumor-cell apoptosis that does not require DC-tumor cell contact and is partially mediated by nitric oxide.
Shimamura
Hiromune
H
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, U.S.A.
Cumberland
Rachel
R
Hiroishi
Kazumasa
K
Watkins
Simon C
SC
Lotze
Michael T
MT
Baar
Joseph
J
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000502:physiology; D002450:Cell Communication; D003713:Dendritic Cells / Q000276:immunology*; D053222:Fas Ligand Protein; D016898:Interferon-alpha / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D009569:Nitric Oxide / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D009569:Nitric Oxide; D002118:Calcium