Lymphokine-activated killer cytotoxicity against pancreas adenocarcinoma cell lines and vascular endothelial cells.
Eight pancreas carcinoma cell lines of duct cell origin (PCI-6, 10, 19, 24, 35, 43, 55, and 64) were established. Using one of these lines, PCI-24, human umbilical vein endothelial cells (HUVEC), and several recombinant cytokines, conditions and specificity of anti-PCI LAK induction were investigated, with the focus on a search for lymphokine-activated killer (LAK) activity that differentiates neoplastic (PCI) from non-neoplastic (HUVEC) cells. Interferon-gamma (IFN-gamma), IFN-alpha, IL-4, IL-6, and IL-7, but not tumor necrosis factor-alpha (TNF-alpha) or IL-1 beta, induced a weak LAK activity against PCI-24, whereas IL-2-induced (1000 U/mL) LAK exhibited a far more potent cytotoxicity. When these cytokines were added at the suboptimal dose IL-2 (100 U/mL), no significant augmentation in LAK activity was induced. Staphylococcal protein A (SpA) induced LAK activity as potent as that seen with IL-2 (1000 U/mL). Both IL-2-induced and SpA-induced LAK had a potent, dose-dependent cytotoxicity against HUVEC. HUVEC inhibited both IL-2- and SpA-induced LAK cytotoxicity against PCI-24 to almost the same extent as seen with PCI-24. Thus, two potent LAK-inducers did not generate LAK activity that differentiates neoplastic from non-neoplastic cells. Thus, in vitro cytotoxicity of LAK against non-neoplastic endothelial cells is unavoidable when handling cytokines in LAK induction.
Sugiura
H
H
Department of Pathology, Hokkaido University, School of Medicine, Sapporo, Japan.
Ishikura
H
H
Omi
M
M
Kaji
M
M
Iwai
K
K
Kishimoto
T
T
Takahashi
T
T
Kimura
C
C
Kato
H
H
Yoshiki
T
T
D000230:Adenocarcinoma / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007376:Interleukin-2