Effects of L2C leukemia on macrophage-mediated responses

Preliminary experiments have suggested that guinea pig L2C B-cell leukemia cells were able to evade macrophage-mediated lysis. To determine whether the L2C cells were resistant to macrophage cytotoxic activity or whether factors associated with the L2C leukemia contributed to a generalized inhibition of macrophage cytotoxic activity, pulmonary macrophages from strain 2 guinea pigs with L2C leukemia were tested for their ability to lyse the susceptible K562 cell line after activation by lipopolysaccharide (LPS) or lymphokines. In addition, the potential presence of soluble inhibitors of macrophage tumoricidal activity in serum-free culture supernatants and in serum from strain 2 guinea pigs terminally ill with the leukemia was tested by determining the effects of leukemic guinea pig serum (LGPS) or L2C-conditioned medium (CM) on the tumoricidal activity of normal pulmonary macrophages. Macrophages from guinea pigs terminally ill with L2C leukemia were demonstrated to be depressed in their cytotoxic activity against the K562 cell after stimulation by either LPS or lymphokines when compared to normal macrophages. The lymphokine-stimulated cytotoxic activity of normal macrophages was inhibited in the presence of LGPS or CM. Oxidative burst activity of normal macrophages, as measured by zymosan-stimulated production of superoxide and hydrogen peroxide, was also inhibited under these conditions. The data presented here suggests that soluble factors associated with L2C leukemia cells can suppress oxidative burst activity of macrophages in vitro and that this effect may contribute to the ability of the leukemia cells to evade macrophage-mediated cytotoxicity.