THE EFFECTS OF SILICA AND FLY ASH ON ALVEOLAR MACROPHAGE EFFECTOR CELL FUNCTION.

摘要

Intratracheal injection (IT) of silica or fly ash into Syrian golden hamsters caused significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC); however, the percent macrophages neutrophils and lymphocytes did not change with particulate injection. IT injection of silica in BCG-primed hamsters was found to activate alveolar macrophages to become tumoricidal against hamster H50 tumor cells, whereas IT injection of silica or BCG-priming alone did not cause activation. IT injection of fly ash in BCG-primed hamsters was found to activate alveolar macrophages to become cytotoxic against H50s to an even greater degree than IT injection of silica.; Inhalation of silica was found to cause significant enhancement of ADCC function after 14, 42 and 70 days, and a significant increase in cells recruited into the lung. Inhalation of fly ash, on the other hand, caused significant suppression of ADCC after 42 days of exposure, and a corresponding decrease in the number of cells recruited into the lung. Both silica inhalation and fly ash inhalation compromised the ability of BCG-primed/BCG-rechallenged alveolar macrophages to mediate tumor cell lysis; however, fly ash exposure caused a less severe suppression of macrophage-mediated cytotoxicity (MMC) than silica exposure. Fly ash exposure also significantly suppressed activated alveolar macrophage lysis by the ADCC mechanism. In the T cell mitogenesis assay, silica inhalation suppressed accessory cell function initially, while fly ash caused significant enhancement of T cell mitogenesis.; When alveolar macrophage subpopulations were examined, it was found that silica caused the HBSS-extracted (HE) subpopulation to respond with enhanced ADCC and less efficient accessory cell function, and the lidocaine-extracted (LE) subpopulation to respond with suppressed ADCC and more efficient accessory cell function. Fly ash caused the HE subpopulation to respond with suppressed ADCC function and more efficient T cell mitogenesis, while the fly ash LE alveolar macrophage subpopulation responded similarly to control LE alveolar macrophages in ADCC, and less efficient in enhancing T cell mitogenesis with PHA. Thus, not only are there heterogeneous alveolar macrophage populations, but these subpopulations respond significantly different according to the nature of particulate stress.