INHALATION COEXPOSURE TO CARBON-BLACK AND ACROLEIN SUPPRESSES ALVEOLAR MACROPHAGE PHAGOCYTOSIS AND TNF-ALPHA RELEASE AND MODULATES PERITONEAL MACROPHAGE PHAGOCYTOSIS
Gj. Jakab et Dr. Hemenway, INHALATION COEXPOSURE TO CARBON-BLACK AND ACROLEIN SUPPRESSES ALVEOLAR MACROPHAGE PHAGOCYTOSIS AND TNF-ALPHA RELEASE AND MODULATES PERITONEAL MACROPHAGE PHAGOCYTOSIS, Inhalation toxicology, 5(3), 1993, pp. 275-289
Acrolein, a hydrophilic vapor that is efficiently absorbed in the uppe
r respiratory tract, is often emitted with respirable particles by com
bustion sources. If acrolein is adsorbed on respirable particles it ma
y be deposited in the deep lung and interact with cells in the lung pa
renchyma. To test this hypothesis, mice were coexposed to target conce
ntrations 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 lipopoly
saccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) produ
ction were assessed. AM phagocytosis was suppressed at 1 through 11 da
ys 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 t
arget 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 pe
rformed at 4 days after cessation of exposure resulted in an initial s
uppression 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 mod
ulatory effect on peritoneal macrophage (PM) phagocytosis. An initial
enhancement for approximately a week after exposure was followed by su
ppression of PM phagocytosis. These data indicate the importance of th
e interaction of acrolein with an inert particle and that the pulmonar
y toxicity of acrolein may depend on its ability to bypass the absorpt
ive surfaces of the upper respiratory tract, thereby allowing it to re
ach the alveolar region of the lung. In addition, the data also point
toward the potential adverse systemic effects of acrolein inhalation.