IMMUNOTOXICITY OF PARTICULATE LEAD - IN-VITRO EXPOSURE ALTERS PULMONARY MACROPHAGE TUMOR-NECROSIS-FACTOR PRODUCTION AND ACTIVITY

Rabbit pulmonary macrophages were exposed in vitro to particulate lead oxide (PbO) for periods of vp to 72 h and then assayed for the activity of tumor necrosis factor-alpha (TNF alpha) released after stimulation with lipopolysaccharide (LPS). The levels of TNF alpha obtained from PbO-treated cells were decreased in a dose-dependent manner as compared with metal-free control cells for each rime point examined. Cells treated simultaneously with both LPS and PbO yielded less monokine than did cells receiving LPS alone. In addition, incubation of cell-free TNF alpha with PbO resulted in a diminution of cytotoxicity directed against TNF alpha-sensitive tumor target cells. Macrophage burdens of PbO particles increased with both the length of incubation and concentration of PbO used; increases in cellular lead burdens were paralleled by reductions in cell viability. Thus, under in vitro conditions, PbO affects the levels of the immunoregulatory monokine TNF alpha and also disrupts its cytotoxic properties after release from activated macrophages.