The toxicologic interactions resulting from inhalation of carbon black and acrolein on pulmonary antibacterial and antiviral defenses.
The goal of this study was to investigate whether coexposures to carbon black and acrolein result in a toxicologic interaction having effects on lung defenses against infectious agents. This aim was accomplished through in vivo studies with inhalation challenges of infectious agents that probe the functional integrity of the multicomponent system that comprises the integrated defenses of the lungs. Staphylococcus aureus was used for the alveolar macrophage (AM) surveillance phagocytic system, Proteus mirabilis for the dual phagocytic system composed of AMs and inflammatory polymorphonuclear leukocytes (PMNs), Listeria monocytogenes for the lymphokine-mediated arm of the acquired cellular immune response, and influenza A virus for the cytotoxic T-cell-mediated effector mechanism of cellular immunity. Exposures of Swiss mice to target concentrations of 10 mg/m3 of carbon black and 2.5 ppm acrolein for 4 hr/day for 4 days suppressed the intrapulmonary killing of S. aureus a day after exposure with a return to control levels by Day 7. In contrast, the coexposure enhanced the intrapulmonary killing of P. mirabilis which correlated with a significant increase in accessory phagocytic PMNs recovered from the lungs. Combined exposure to carbon black and acrolein also resulted in impaired elimination of L. monocytogenes and influenza A virus from the lungs. Neither exposure to carbon black alone nor exposure to acrolein alone had any effect on the functional integrity of lung defenses against the four infectious agents. These data demonstrate the effects of the toxicologic interaction of coexposures to an inert particle and acrolein on innate and acquired defenses of the lungs. The mechanism for the enhanced biologic effect may be that the carbon black particle acts as a carrier mechanism for acrolein to the deep lung.
Jakab
G J
GJ
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000280:Administration, Inhalation; D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002244:Carbon / Q000008:administration & dosage / Q000633:toxicity*; D003141:Communicable Diseases / Q000276:immunology / Q000382:microbiology; D004347:Drug Interactions; D005260:Female; D008089:Listeria monocytogenes / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008815:Mice, Inbred Strains; D009975:Orthomyxoviridae / Q000187:drug effects; D011513:Proteus mirabilis / Q000187:drug effects; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects
D000418:Albumins; D002244:Carbon; D000171:Acrolein