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

Intralobular injection of 0.17 ml of 2% carrageenan, through a ventral slit in the trachea of rats, induced localised areas of inflammation with a high survival rate. This inflammation was characterised by immediate polymorphonuclear leucocyte (PMN) infiltration into the interstitial and alveolar spaces followed in 4 days by replacement of the PMNs by carrageenan-containing macrophages. Between days 10 to 70, the macrophages rapidly increased in size and accumulated numerous large vacuoles which stained for the presence of carrageenan. Several macrophages were so large that they each filled an entire alveolar space. From days 70 to 205, the macrophage appearance was unchanged except that the staining of their carrageenan-containing vacuoles was less metachromatic with toluidine blue. Fibrosis was first noted at day 205 and consisted of several small granulomas located near large airways and blood vessels. These granulomas had a central area filled with macrophages and a peripheral zone consisting of fibroblasts, new collagen, scattered macrophages and blood vessels. The morphology of the macrophages remained essentially unchanged from days 205 to 500 but by day 500, the macrophages were found only in numerous pockets within the inflamed lobe. They still stained positive for the presence of carrageenan at day 500. The extreme longevity of these macrophages and the lack of significant fibrosis may be due to the "un-naturalness", indigestibility, and low toxicity of the irritant, carrageenan. In addition, their size and numerous vacuoles may have inhibited their movement and subsequent removal from the lung. The paucity of significant fibrosis may be due to the lack or inhibition of a "fibroblast stimulating factor" released by the macrophages or possibly the collagen was degraded as soon as it was synthesised. This carrageenan-induced inflammation is a very suitable for the study of alveolar macrophages but appears to be inappropriate for the study of pulmonary fibrosis.