INHALATION COEXPOSURE TO CARBON-BLACK AND ACROLEIN SUPPRESSES ALVEOLAR MACROPHAGE PHAGOCYTOSIS AND TNF-ALPHA RELEASE AND MODULATES PERITONEAL MACROPHAGE PHAGOCYTOSIS

Acrolein, a hydrophilic vapor that is efficiently absorbed in the upper respiratory tract, is often emitted with respirable particles by combustion sources. If acrolein is adsorbed on respirable particles it may be deposited in the deep lung and interact with cells in the lung parenchyma. To test this hypothesis, mice were coexposed to target concentrations of 10 mg/m3 of carbon black and 2.5 ppm acrolein for 4 hours/day for 4 days and alveolar macrophage (AM) phagocytosis and lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) production were assessed. AM phagocytosis was suppressed at 1 through 11 days after exposure, with recovery of phagocytic activity at day 20. TNF-alpha production was also initially impaired but was reestablished by day 20. Suppression of AM phagocytosis and TNF-alpha production were not observed following exposure to either agent alone. Coexposure to target concentrations of 10 mg/m3 of carbon black and 5 ppm of acrolein for 4 hours/day for either 2, 4, 6, or 8 days with AM phagocytosis performed at 4 days after cessation of exposure resulted in an initial suppression of phagocytosis followed by an adaptive response, as shown by reestablishment of phagocytosis with prolonged exposure. Coexposure to carbon black and acrolein or acrolein alone also resulted in a modulatory effect on peritoneal macrophage (PM) phagocytosis. An initial enhancement for approximately a week after exposure was followed by suppression of PM phagocytosis. These data indicate the importance of the interaction of acrolein with an inert particle and that the pulmonary toxicity of acrolein may depend on its ability to bypass the absorptive surfaces of the upper respiratory tract, thereby allowing it to reach the alveolar region of the lung. In addition, the data also point toward the potential adverse systemic effects of acrolein inhalation.