Tumoricidal activation of murine resident peritoneal macrophages by interleukin 2 and tumor necrosis factor alpha.
The capacity of recombinant human interleukin 2 (rH-IL2), alone or in combination with recombinant tumor necrosis factor (r-TNF alpha), to activate murine resident peritoneal macrophages to a tumoricidal state was examined. Resident peritoneal exudate cells from C57BL/6 mice were cultured for 18 h with activating agents and washed and the adherent cells (macrophages) were assessed for cytolytic activity against radiolabeled target tumor cells (EL4, P815). Under these conditions, rH-IL2 alone activated macrophages to a tumoricidal state in a concentration dependent fashion. Neither murine nor human r-TNF alpha alone had any activating effect but, when combined with rH-IL2, further stimulated rH-IL2-inducible responses. Using polymyxin B, it was shown that macrophage activation was not due to an inadvertent lipopolysaccharide contamination of the r-TNF alpha or rH-IL2 preparations. It was also unlikely that target cell lysis was a direct result of increased TNF alpha production by rH-IL2 stimulated macrophages since P815 is totally resistant to lysis by r-TNF alpha. Although the lytic effector function was mediated by adherent cells, nonadherent peritoneal exudate cells were required for activation to occur. Furthermore, antisera against murine gamma-interferon, when added to activation cultures, reduced the level of cytolytic activity which developed. These data suggest that rH-IL2-induced peritoneal macrophage activation requires stimulation of nonadherent cells and is dependent upon gamma-interferon mediated mechanisms.
Verstovsek
S
S
Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263.
Maccubbin
D
D
Ehrke
M J
MJ
Mihich
E
E
D000818:Animals; D004357:Drug Synergism; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D016399:Lymphoma, T-Cell / Q000628:therapy; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects*; D012515:Mast-Cell Sarcoma / Q000628:therapy; D009374:Neoplasms, Experimental / Q000628:therapy*; D010529:Peritoneal Cavity / Q000166:cytology; D011112:Polymyxin B / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011112:Polymyxin B