Chrysotile asbestos exposures can produce an alveolitis with limited fibrosing activity in a subset of high fibre retainer sheep

Abstract

Inhalation of fibrogenic mineral dust may enhance fibronectin (Fn) production by alveolar macrophages and increase fibroblast growth activity (FGA) in lung lavage fluid. To investigate the relationship of these changes to fibre retention and the development of asbestosis, we exposed 15 sheep to 100 mg Canadian chrysotile fibres in 100 ml saline, and ten sheep to 100 ml saline only, at ten day intervals. The animals were studied at 3 month intervals. At month 18, ten sheep had abnormal chest radiograph (category greater than or equal to 1) (group B) and five had normal radiograph (category 0) (group A). Pulmonary function data indicated restrictive patterns of abnormalities in both groups, more severe in group B. Sheep in group A had bronchoalveolar lavage (BAL) cellularity and biochemistry comparable to controls; sheep in group B had significant increases in total BAL cells (x2), macrophages (x2), neutrophils (x4) and eosinophils (x3), increased BAL lactate dehydrogenase and Fn, but FGA and procollagen 3 comparable to controls. Fibre retention was significantly increased in all exposed sheep and 2.5 x higher in group B vs group A despite similar exposures (70 intratracheal, 100 mg chrysotile infusions). Enhanced fibre retention in group B preceded the appearance of disease. This study confirms our earlier observation linking individual susceptibility to development of alveolitis to individual dust burden and provides evidence that the excess of fibre retention can be observed before detectable disease. In addition, we report a chrysotile-induced early alveolitis with incompletely expressed fibrosing activity at the time of initial radiographic detection. The intensity of the alveolitis is related to the degree of fibre retention.