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Toxicologic Pathology
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Journal Article

Carbon Tetrachloride-Induced Hepatotoxicity Enhances the Development of Pulmonary Foam Cells in Rats Fed a Cholesterol-Cholic Acid Diet

Kazumoto Shibuya

Nippon Institute for Biological Science, 2221-1 Shinmachi, Ome, Tokyo 198, Japan

Masanori Tajima

Nippon Institute for Biological Science, 2221-1 Shinmachi, Ome, Tokyo 198, Japan

Jyoji Yamate

Nippon Institute for Biological Science, 2221-1 Shinmachi, Ome, Tokyo 198, Japan

Toshiki Saitoh

Nippon Institute for Biological Science, 2221-1 Shinmachi, Ome, Tokyo 198, Japan

Tetsuo Nunoya

Nippon Institute for Biological Science, 2221-1 Shinmachi, Ome, Tokyo 198, Japan

The effect of CCl 4-hepatotoxicity on the development of pulmonary foam cells (PFCs) was studied using 4 groups of rats. Rats in the control group were fed a standard diet; rats in the second group were fed a hyper β-lipoproteinemic (HB) diet consisting of the standard diet, 4% cholesterol, and 1% cholic acid; rats in the third group were fed the standard diet and administered with CCl4 (1.0 ml/kg, ip, fortnightly) (CT); and rats in the fourth group were fed the HB diet and administered with CCl4 (HT). At feeding week 10, rats in the HB and HT groups developed hyper β-lipoproteinemia. The ratios of foamy, lipid-ingested monocytes (FMs) to blood monocytes (BMs) and the histologic scores of PFC development were significantly greater in the HB and HT groups than in the control and CT groups, respectively. The ratio of PFCs to alveolar macrophages from bronchopulmonary lavage fluid was significantly higher in the HT group than in the CT group. At feeding week 20, rats in the CT and HT groups suffered hepatic injury and hypo β-lipoproteinemia. Despite hypo β-lipoproteinemia, the FM and PFC development, the ratio of BMs in differential leukocyte counts, and latex-phagocytotic activity of BMs were enhanced in the HT group. Furthermore, markedly enlarged FMs, described here as giant-FMs, that contained numerous lipid droplets in their abundant cytoplasm appeared in the peripheral blood from rats in the HT group. Histologically, embolism caused by giant-FMs in the pulmonary blood vessels and intraalveolar accumulation of PFCs were detected with a high incidence in the HT group. The present study suggests that CCl4-hepatotoxicity may affect lipoprotein synthesis in the liver of hyper β-lipoproteinemic rats and defective or modified lipoproteins can be phagocytosed actively by BMs, and then BMs transform into FMs or giant-FMs, resulting in the PFC development and pulmonary embolism by giant-FMs.

Key Words: Cytology • fat embolism • foamy transformation • hepatic injury • histopathology • lipoprotein • monocyte • phagocytosis

Toxicologic Pathology, Vol. 25, No. 5, 487-494 (1997)
DOI: 10.1177/019262339702500510
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