Abstract
Administration of amphophilic drugs to experimental animals causes formation of myeloid bodies in many cell types, accumulation of foamy macrophages in pulmonary alveoli, and pulmonary alveolar proteinosis. These changes are the result of an interaction between the drugs and phospholipids which leads to an alteration in physicochemical properties of the phospholipids. Impairment of the digestion of altered pulmonary secretions in phagosomes of macrophages results in accumulation of foam cells in pulmonary alveoli. Impairment of the metabolism of altered phospholipids removed by autophagy induces an accumulation of myeloid bodies. In summary, administration of amphophilic compounds causes a drug-induced lysosomal disease or generalized phospholipidosis.
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- Abraham R., Hendy R. Effects of chronic chloroquine treatment on lysosomes of rat liver cells. Exp Mol Pathol. 1970 Apr;12(2):148–159. doi: 10.1016/0014-4800(70)90046-8. [DOI] [PubMed] [Google Scholar]
- Brewer D. B., Heath D., Asquith P. Electron microscopy of desquamative interstitial pneumonia. J Pathol. 1969 Feb;97(2):317–323. doi: 10.1002/path.1710970217. [DOI] [PubMed] [Google Scholar]
- Corrin B., King E. Experimental endogenous lipid pneumonia and silicosis. J Pathol. 1969 Feb;97(2):325–330. doi: 10.1002/path.1710970218. [DOI] [PubMed] [Google Scholar]
- Corrin B., Price A. B. Electron microscopic studies in desquamative interstitial pneumonia associated with asbestos. Thorax. 1972 May;27(3):324–331. doi: 10.1136/thx.27.3.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davidson J. M., Macleod W. M. Pulmonary alveolar proteinosis. Br J Dis Chest. 1969 Jan;63(1):13–28. doi: 10.1016/s0007-0971(69)80040-9. [DOI] [PubMed] [Google Scholar]
- De la Iglesia F. A., Feuer G., Takada A., Matsuda Y. Morphologic studies on secondary phospholipidosis in human liver. Lab Invest. 1974 Apr;30(4):539–549. [PubMed] [Google Scholar]
- Dietert S. E., Scallen T. J. An ultrastructural and biochemical study of the effects of three inhibitors of cholesterol biosynthesis upon murine adrenal gland and testis. Histochemical evidence for a lysosome response. J Cell Biol. 1969 Jan;40(1):44–60. doi: 10.1083/jcb.40.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eichelbaum M., Hengstmann J. H., Dengler H. J. Das Verteilungsmuster des Chlorphentermins bei Ratte, Kaninchen und Schwein. Naunyn Schmiedebergs Arch Pharmakol. 1970;267(5):446–456. [PubMed] [Google Scholar]
- Farr G. H., Harley R. A., Hennigar G. R. Desquamative interstitial pneumonia. An electron microscopic study. Am J Pathol. 1970 Sep;60(3):347–370. [PMC free article] [PubMed] [Google Scholar]
- Flaks B., Flaks A. Electron-microscope observations on the formation of the cytoplasmic lamellar inclusion bodies in murine pulmonary tumours induced in vitro. J Pathol. 1972 Nov;108(3):211–217. doi: 10.1002/path.1711080307. [DOI] [PubMed] [Google Scholar]
- Flodh H., Magnusson G. Genesis of foam cells: study in rats after administration of Cloforex. Virchows Arch B Cell Pathol. 1973 Mar 30;12(4):360–366. doi: 10.1007/BF02894012. [DOI] [PubMed] [Google Scholar]
- Flodh H., Magnusson G., Magnusson O. Pulmonary foam cells in rats of different age. Z Versuchstierkd. 1974;16(4-5):299–312. [PubMed] [Google Scholar]
- Franken G., Lüllmann H., Siegfriedt A. The occurrence of huge cells in pulmonary alveoli of rats treated by an anorexic drug. Arzneimittelforschung. 1970 Mar;20(3):417–417. [PubMed] [Google Scholar]
- Gray J. E., Purmalis A., Purmalis B., Mathews J. Ultrastructural studies of the hepatic changes brought about by Clindamycin and Erythromycin in animals. Toxicol Appl Pharmacol. 1971 Jun;19(2):217–233. doi: 10.1016/0041-008x(71)90108-6. [DOI] [PubMed] [Google Scholar]
- Greselin E. An inhibitor of cholesterol biosynthesis and the alveolar macrophages. Can J Comp Med Vet Sci. 1966 May;30(5):121–126. [PMC free article] [PubMed] [Google Scholar]
- Heppleston A. G., Wright N. A., Stewart J. A. Experimental alveolar lipo-proteinosis following the inhalation of silica. J Pathol. 1970 Aug;101(4):293–307. doi: 10.1002/path.1711010402. [DOI] [PubMed] [Google Scholar]
- Hoffmann E. O., Lamberty J., Pizzolato P., Coover J. The ultrastructure of acute silicosis. Arch Pathol. 1973 Aug;96(2):104–107. [PubMed] [Google Scholar]
- Hruban Z., Swift H., Slesers A. Effect of triparanol and diethanolamine on the fine structure of hepatocytes and pancreatic acinar cells. Lab Invest. 1965 Sep;14(9):1652–1672. [PubMed] [Google Scholar]
- Ito S., Tsukada Y. Clinico-pathological and electron microscopical studies on a coronary dilating agent: 4-4'-diethylaminoethoxyhexestrol-induced liver injuries. Acta Hepatogastroenterol (Stuttg) 1973 May-Jun;20(3):204–215. [PubMed] [Google Scholar]
- Kikkawa Y., Suzuki K. Alteration of cellular and acellular alveolar and bronchiolar walls produced by hypocholesteremic drug AY9944. Lab Invest. 1972 Apr;26(4):441–447. [PubMed] [Google Scholar]
- Kitani T., Yamamoto A., Adachi S., Tako H., Imanaka T. [Drug-induced lipidosis. IV. Morphological aspect of leukocytes and bone marrow cells in human cases and animal experiments induced by 4,4'-diethylaminoethoxy-hexestrol]. Nihon Ketsueki Gakkai Zasshi. 1972 Apr;35(2):131–145. [PubMed] [Google Scholar]
- Kuhn C., Györkey F., Levine B. E., Ramirez-Rivera J. Pulmonary alveolar proteinosis. A study using enzyme histochemistry, electron microscopy, and surface tension measurement. Lab Invest. 1966 Feb;15(2):492–509. [PubMed] [Google Scholar]
- Le Beux Y., Hetenyi G., Jr, Phillips M. J. Mitochondrial myelin-like figures: a non-specific reactive process of mitochondrial phospholipid membranes to several stimuli. Z Zellforsch Mikrosk Anat. 1969;99(4):491–506. doi: 10.1007/BF00340941. [DOI] [PubMed] [Google Scholar]
- Littler W. A., Kay J. M., Hasleton P. S., Heath D. Busulphan lung. Thorax. 1969 Nov;24(6):639–655. doi: 10.1136/thx.24.6.639. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lúllmann-Rauch R., Reil G. H. Fenfluramine-induced ultrastructural alterations in tissues of rats and guinea pigs. Naunyn Schmiedebergs Arch Pharmacol. 1974;285(2):175–184. doi: 10.1007/BF00501152. [DOI] [PubMed] [Google Scholar]
- Lüllmann Rauch R., Reil G. H. Chlorphentermine-induced lipidosislike ultrastructural alterations in lungs and adrenal glands of several species. Toxicol Appl Pharmacol. 1974 Dec;30(3):408–421. doi: 10.1016/0041-008x(74)90263-4. [DOI] [PubMed] [Google Scholar]
- Lüllmann-Rauch R., Pietschmann N. Lipidosis-like cellular alterations in lymphatic tissues of chlorphentermine-treated animals. Virchows Arch B Cell Pathol. 1974;15(4):295–308. doi: 10.1007/BF02889345. [DOI] [PubMed] [Google Scholar]
- Lüllmann-Rauch R., Reil G. H. Chlorphentermine-induced ultrastructural changes in liver tissues of four animal species. Virchows Arch B Cell Pathol. 1973 Aug 21;13(4):307–320. doi: 10.1007/BF02889316. [DOI] [PubMed] [Google Scholar]
- Lüllmann-Rauch R., Reil G. H., Rossen E., Seiler K. U. The ultrastructure of rat lung changes induced by an anorectic drug (chlorphentermine). Virchows Arch B Cell Pathol. 1972;11(2):167–181. doi: 10.1007/BF02889396. [DOI] [PubMed] [Google Scholar]
- Lüllmann-Rauch R., Reil G. H., Scheid D. Lipidosis-ähnliche Zellveränderungen bei der Ratte nach Behandlung mit Thymoleptika. Verh Dtsch Ges Pathol. 1973;57:425–425. [PubMed] [Google Scholar]
- Mielke H., Seiler K. U., Stumpf U., Wassermann O. Uber eine Beziehung zwischen dem Serotoninstoffwechsel und der pulmonalen Hypertonie bei Ratten nach Gabe verschiedener Anorektika. Z Kardiol. 1973 Dec;62(12):1090–1098. [PubMed] [Google Scholar]
- OLINER H., SCHWARTZ R., RUBIO F., DAMESHEK W. Interstitial pulmonary fibrosis following busulfan therapy. Am J Med. 1961 Jul;31:134–139. doi: 10.1016/0002-9343(61)90229-7. [DOI] [PubMed] [Google Scholar]
- Parwaresch R., Reil G. H., Seiler K. U. Uber die Tier- und Organspezifität morphologischer Veränderungen nach chronischer Chlorphentermingabe. Res Exp Med (Berl) 1973 Nov 23;161(4):272–288. doi: 10.1007/BF01851451. [DOI] [PubMed] [Google Scholar]
- Pattle R. E., Schock C., Dirnhuber P., Creasey J. M. Lung surfactant and organelles after an exposure to dibenzoxazepine (CR). Br J Exp Pathol. 1974 Jun;55(3):213–220. [PMC free article] [PubMed] [Google Scholar]
- ROSEN S. H., CASTLEMAN B., LIEBOW A. A. Pulmonary alveolar proteinosis. N Engl J Med. 1958 Jun 5;258(23):1123–1142. doi: 10.1056/NEJM195806052582301. [DOI] [PubMed] [Google Scholar]
- Read W. K., Bay W. W. Basic cellular lesion in chloroquine toxicity. Lab Invest. 1971 Mar;24(3):246–259. [PubMed] [Google Scholar]
- Rhodes M. L. Desquamative interstitial pneumonia. New ultrastructural findings. Am Rev Respir Dis. 1973 Oct;108(4):950–954. doi: 10.1164/arrd.1973.108.4.950. [DOI] [PubMed] [Google Scholar]
- Ryrfeldt A. The distribution, elimination, and biotransformation of 14C-cloforex in the mouse and rat. Acta Pharmacol Toxicol (Copenh) 1970;28(5):391–405. doi: 10.1111/j.1600-0773.1970.tb00565.x. [DOI] [PubMed] [Google Scholar]
- Schmien R., Seiler K. U., Wassermann O. Drug-induced phospholipidosis. I. Lipid composition and chlorphentermine content of rat lung tissue and alveolar macrophages after chronic treatment. Naunyn Schmiedebergs Arch Pharmacol. 1974;283(3):331–334. doi: 10.1007/BF00499192. [DOI] [PubMed] [Google Scholar]
- Seiler K. U., Wassermann O. Drug-induced phospholipidosis. II. Alterations in the phospholipid pattern of organs from mice, rats and guinea-pigs after chronic treatment with chlorphentermine. Naunyn Schmiedebergs Arch Pharmacol. 1975;288(2-3):261–268. doi: 10.1007/BF00500531. [DOI] [PubMed] [Google Scholar]
- Shikata T., Kanetaka T., Endo Y., Nagashima K. Drug-induced generalized phospholipidosis. Acta Pathol Jpn. 1972 Aug;22(3):517–531. doi: 10.1111/j.1440-1827.1972.tb01849.x. [DOI] [PubMed] [Google Scholar]
- Shortland J. R., Darke C. S., Crane W. A. Electron microscopy of desquamative interstitial pneumonia. Thorax. 1969 Mar;24(2):192–208. doi: 10.1136/thx.24.2.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith P., Heath D., Hasleton P. S. Electron microscopy of chlorphentermine lung. Thorax. 1973 Sep;28(5):559–566. doi: 10.1136/thx.28.5.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vijeyaratnam G. S., Corrin B. Fine structural alterations in the lungs of iprindole-treated rats. J Pathol. 1974 Dec;114(4):233–240. doi: 10.1002/path.1711140408. [DOI] [PubMed] [Google Scholar]
- Vijeyaratnam G. S., Corrin B. Origin of the pulmonary alveolar macrophage studied in the iprindole-treated rat. J Pathol. 1972 Oct;108(2):115–118. doi: 10.1002/path.1711080204. [DOI] [PubMed] [Google Scholar]
- Vijeyaratnam G. S., Corrin B. Pulmonary alveolar proteinosis developing from desquamative interstitial pneumonia in long term toxicity studies of iprindole in the rat. Virchows Arch A Pathol Pathol Anat. 1973;358(1):1–10. doi: 10.1007/BF00555550. [DOI] [PubMed] [Google Scholar]
- Vijeyaratnam G. S., Corrin B. Pulmonary histiocytosis simulating desquamative interstitial pneumonia in rats receiving oral iprindole. J Pathol. 1972 Oct;108(2):105–113. doi: 10.1002/path.1711080203. [DOI] [PubMed] [Google Scholar]
- Yates R. D., Arai K., Rappoport D. A. Fine structure and chemical composition of opaque cytoplasmic bodies of triparanol treated Syrian hamsters. Exp Cell Res. 1967 Sep;47(3):459–478. doi: 10.1016/0014-4827(67)90004-3. [DOI] [PubMed] [Google Scholar]