Indicator Of Pulmonary Injury Research Articles

SOLUBLE TRANSITION METALS MEDIATE RESIDUAL OIL FLY ASH INDUCED ACUTE LUNG INJURY

Identification of constituents responsible for the pulmonary toxicity of fugitive combustion emission source particles may provide insight into the adverse health effects associated with exposure to these particles as well as ambient air particulate pollution. Herein, we describe results of studies conducted to identify constituents responsible for the acute lung injury induced by residual oil fly ash (ROFA) and to assess physical-chemical factors that influence the pulmonary toxicity of these constituents. Biochemical and cellular analyses performed on bronchoalveolar lavage fluid obtained from rats following intratracheal instillation of ROFA suspension demonstrated the presence of severe inflammation, an indicator of pulmonary injury, which included recruitment of neutrophils, eosinophils, and monocytes into the airway. A leachate prepared from ROFA, containing predominantly Fe, Ni, V, Ca, Mg, and sulfate, produced similar lung injury to that induced by ROFA suspension. Depletion of Fe, Ni, and V from the ROFA leachate abrogated its pulmonary toxicity. Correspondingly, minimal lung injury was observed in animals exposed to saline-washed ROFA particles. A surrogate transition metal sulfate solution containing Fe, V, and Ni largely reproduced the lung injury induced by ROFA. Metal interactions and pH were found to influence the severity and kinetics of lung injury induced by ROFA and soluble transition metals. These findings provide direct evidence for the role of soluble transition metals in the pulmonary injury induced by the combustion emission source particulate, ROFA.

N-acetyl-beta-D-glucosaminidase activity within BAL from macaques exposed to generic coal dusts

N-acetyl-beta(beta)-D-glucosaminidase is a lysosomal enzyme secreted by alveolar macrophages in response to phagocytosis of particulate material. Alveolar macrophages participate in the degradation and fibrosis of pulmonary tissue that results in pneumoconiosis. Known quantities of four characterized respirable dusts were bronchoscopically placed into the right caudal lung lobe of macaque monkeys. Bronchoalveolar lavage (BAL) samples were collected from dust-exposed right lung and unexposed left lung of the same individuals at 2-week intervals for 12 weeks after dust instillation. The samples were tested for N-acetyl-beta-D-glucosaminidase activity to determine if the enzyme levels could serve as an indicator of pulmonary injury induced by generic coal dusts when compared to known fibrogenic and nuisance dusts. Installation of generic quartz, anthracite, or TiO2 dusts produced significant elevations of enzyme activity and increased numbers of macrophages in the dust-exposed lobes. Elevations in enzymatic activity and macrophage numbers were greatest in response to generic quartz dust. These results suggest that quantitative levels of N-acetyl-beta-D-glucosaminidase activity may be a useful indicator of acute and chronic lung injury following exposure to fibrogenic and nonfibrogenic dusts.

Effect of pneumotoxicants on lactate dehydrogenase activity in airways of rats

To assess the usefulness of monitoring changes in lactate dehydrogenase (LDH) activity in the cell-free fraction of bronchopulmonary lavage fluid as an indicator of pulmonary injury, several toxicants were administered to rats using treatment regimens which have been shown previously to result in histopathologically demonstrable pneumotoxicity. For all of the toxicants employed except exposure to 1 atm O 2, treatment did not affect recovery of lavage fluid from the lung. Lavage fluid LDH activity was elevated following treatment with paraquat, bromobenzene, and oxygen. Administration of monocrotaline using a treatment regimen which results predominantly in lung injury also produced elevated LDH activity in lavage fluid; however, treatment with this same compound using a regimen which results predominantly in hepatic injury failed to elevate lavage fluid LDH activity but resulted in a more pronounced increase in LDH activity in plasma. Similarly, the hepatotoxicant, carbon tetrachloride, produced a marked increase in plasma LDH activity without affecting that of the lavage fluid. The sensitivity of this method in detecting increased LDH activity was minimally dependent upon the volume of fluid used for lavage or on the number of successive lavages used for analysis. It appears to be useful as a rapid screening test for detecting lung injury from chemicals which are pneumotoxic following inhalation or systemic administration.

Hyaluronic acid — An indicator of pulmonary injury?

Hyaluronic acid was the only glysosaminoglycan detected in the pulmonary secretions of healthy adult rats exposed by inhalation to methylene chloride, but not of the control animals. The compound migrated as a single spot with the mobility of standard hyaluronic acid on cellulose acetate electrophoresis and disappeared after digestion with testicular hyaluronidase. Its identification was confirmed by finding hexuronate/hexosamine in a molar ratio of approx. 1. Glucosamine represented over 97% of the total hexosamine, the remaining 3% being galactosamine. No hexose or sulfate could be detected. Sodium dodecyl sulfate—polyacrylamide gel electrophoresis showed no protein associated with this glycosaminoglycan. It appears that the secretion of hyaluronic acid into the airways may be the result of pulmonary inflammation induced by the toxic effects of methylene chloride.