Jakab G J
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205.
Toxicol Appl Pharmacol. 1993 Aug;121(2):167-75. doi: 10.1006/taap.1993.1142.
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.
本研究的目的是调查同时接触炭黑和丙烯醛是否会产生毒理学相互作用，从而影响肺部对感染因子的防御能力。该目标是通过对感染因子进行吸入挑战的体内研究来实现的，这些研究可探究构成肺部综合防御的多组分系统的功能完整性。金黄色葡萄球菌用于测试肺泡巨噬细胞（AM）监测吞噬系统，奇异变形杆菌用于测试由AM和炎性多形核白细胞（PMN）组成的双重吞噬系统，单核细胞增生李斯特菌用于测试获得性细胞免疫反应中细胞因子介导的部分，甲型流感病毒用于测试细胞免疫中细胞毒性T细胞介导的效应机制。将瑞士小鼠暴露于目标浓度为10 mg/m3的炭黑和2.5 ppm的丙烯醛中，每天暴露4小时，持续4天，暴露后一天肺部对金黄色葡萄球菌的杀灭作用受到抑制，到第7天恢复到对照水平。相比之下，同时暴露增强了肺部对奇异变形杆菌的杀灭作用，这与从肺部回收的辅助吞噬PMN显著增加相关。同时暴露于炭黑和丙烯醛还导致肺部对单核细胞增生李斯特菌和甲型流感病毒的清除受损。单独暴露于炭黑或单独暴露于丙烯醛对肺部针对这四种感染因子的防御功能完整性均无任何影响。这些数据证明了同时暴露于惰性颗粒和丙烯醛的毒理学相互作用对肺部先天性和获得性防御的影响。生物效应增强的机制可能是炭黑颗粒作为丙烯醛进入深部肺部的载体机制。
