A biochemical study of the carrageenan-induced granuloma in the rat lung.

Intralobular injection of carrageenan in the rat lung induced a chronic granulomatous response, characterized by a prolonged accumulation of macrophages within the affected lobe. This was accompanied by moderate but significant increases in lysosomal beta-acetyl glucosaminidase, cathepsin B1, and neutral protease activity. Beta-acetyl glucosaminidase and cathepsin B1 activities peaked on day 16 post carrageenan injection and cathepsin B1 activity peaked again on day 112. These enzyme peaks correlated with previous morphological findings that numerous PMNs and carrageenan-containing macrophages were present in the alveoli on day 16 and on day 112. Lymphocytes and plasma cells were present in the alveoli on day 112 in addition to the numerous carrageenan-filled large macrophages. The caseinolytic enzyme activity was significantly elevated over controls throughout the duration of the experiment but no distinct peaks of activity were observed. Based on determinations of total collagen, insoluble collagen, salt-soluble collagen, acid-soluble collagen, protein, total proline, and specific activity of proline and hydroxyproline, there was biochemical evidence of increased collagen synthesis or collagen accumulation in the inflamed lobes on days 4 to 32 as compared to the control lobes. No evidence was found to indicate an increase of collagen or collagen synthesis after day 32 in the experimental lobes. These results differ from our earlier histological and ultrastructural findings which reported that no increased collagen deposition was observed on any day in this system, even 500 days post carrageenan injection. Lung to body weight ratios of experimental animals were significantly elevated over controls on all days studied.