Sequential changes of lamellar body hydrolases during ozone-induced alveolar injury and repair

R. H. Glew, A. Basu, S. A. Shelley, J. F. Paterson, W. F. Diven, M. R. Montgomery, J. U. Balis

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Lamellar body hydrolases in acutely damaged and regenerating type II cells were determined using an established rat model with well-defined stages of bronchiolo-alveolar injury and repair. Lamellar bodies were isolated from control and ozone-exposed (3.0 ppm for 8 hours) adult male rats by sucrose density gradient centrifugation and analyzed for their content of six different lysosomal hydrolases. Immediately after 3 ppm ozone exposure (zero-time) there was a significant decrease in specific enzyme activity (units/mg protein) of five lamellar body hydrolases and these activities remained depressed for at least 24 hours after exposure. In addition, total enzyme activity (units/lung) was reduced at zero-time for β-hexosaminidase and at 24 hours postexposure for α-mannosidase and α-L-fucosidase. During the reparative and recovery stages (48 to 96 hours) the hydrolases demonstrated variable elevations in both specific activity and total activity (units/lung). Characteristically, β-hexosaminidase and β-galactosidase reached supranormal values at 96 hours, whereas α-mannosidase remained below normal levels through the recovery stage. Moreover, at 24 to 48 hours the lamellar body fraction demonstrated prominent enzyme depletion relative to the expanding pool of stored surfactant. It is concluded that acute ozone stress initiates the development of hydrolase deficiency within the lamellar bodies of injured and regenerating type II cells. This deficiency state is followed by asynchronous lamellar body hydrolase elevations that reflect distinct patterns of response rather than uniform return to normal condition. The lysosomal enzyme changes of lamellar bodies may be pathogenetically linked to the development of associated alterations in the storage and secretion of surfactant.

Original languageEnglish
Pages (from-to)1143-1150
Number of pages8
JournalAmerican Journal of Pathology
Issue number5
StatePublished - 1989


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