An attempt to evaluate lung aggression in monkey silicosis: hydrolases, peroxidase and antiproteases activities in serial bronchoalveolar lavages

Abstract

Exposure to silica can induce fibrosis and/or emphysema. Various factors such as proteases, other hydrolases and oxidants may be involved in the destruction of lung parenchyma. On the other hand, antiproteases play an important role in the protection of lung parenchyma against the action of proteases. We have developed an animal model of silicosis in monkey Macacus cynomolgus and followed these factors by bronchoalveolar lavage (BAL). We have studied glycosidases activities, elastase-like activity, immunoreactive alpha 1-protease inhibitor (alpha 1PI), neutrophil elastase inhibitory capacity (NEIC) and myeloperoxidase. Bronchoalveolar cells in serial BAL were also studied. Six monkeys were exposed to quartz aerosols (100 mg.m-3) for 18 wks. They were followed until they developed X-ray changes, which occurred between 21-64 wks after the end of the dust exposure. Cellular "silicotic nodules" were observed in lung biopsies. A control animal underwent serial BAL. Changes were seen in the differential cell count. The release of superoxide anion by bronchoalveolar cells obtained during the experiment was increased. Separation on a gradient of Percoll showed the presence of young macrophages, which exhibited enhanced release of superoxide anion as compared to the totality of bronchoalveolar cells. The biochemical analysis of BAL fluids obtained during and after the period of dust exposure showed an increase in glycosidases, alpha 1PI and NEIC. Some free elastase-like activity was simultaneously detected in BAL fluids from exposed animals but not from the control. This elastase-like activity was very low compared to NEIC. The increase in enzymatic and antiprotease activities occurred at different points in time for each animal, suggesting large differences in individual responses to dust, but occurred before the chest X-ray abnormalities.

Mechanisms of mineral dust-induced emphysema.

“…This question has not been extensively investigated. Brown et al (12) showed that there were increases in lavage proteolytic activity from rats given quartz or titanium dioxide, but Hannothiaux et al (13) found only small and inconsistent increases in lavage elastase activity from monkeys administered quartz. Rom (14) reported increased levels of elastase complexed to AlAT in lavages from coal miners.…”

Animal models of silicosis: fishing for new therapeutic targets and treatments

“…At present, animal models are widely used for the reproduction of all different types of human diseases, allowing the deeper study of physical and pathological mechanisms and the search for new therapies and treatments. Silicosis can occur spontaneously in nature and many cases have been reported in numerous mammalian species such as pigs [ 66 ], dogs [ 67 ], camels [ 68 ], horses [ 69 , 70 ], nonhuman primates [ 71 ], river otters [ 72 ] and marsupials [ 73 ]. It has also been found in various species of birds like ground dwelling kiwi ( Apteryx spp.)…”