Abstract
The biochemical and morphological aspects of BALB/c mice with many features of the Niemann-Pick disease type C in man (NP-C mouse) have been studied extensively. However, the pulmonary pathology has not been studied extensively and we describe here some unique ultrastructural features of the lung in the NP-C mouse. Ultrastructurally, macrophages in younger mice contained osmiophilic dense granules and annulolamellar structures, but larger multilamellar concentric structures increased in the macrophages of older mice. In contrast, endothelial cells and type I pneumocytes showed membrane-bound bodies with dense granules and vesicular or vesiculogranular structures as well as amorphous materials. Type II pneumocytes were unremarkable throughout. Our study suggests that endothelial cells and type I pneumocytes are the major site of metabolic derangement resulting in pronounced morphological changes with granular and round membranous structures in the lungs of NP-C mouse. Alveolar macrophages with multilamellar concentric structures may be a result of disturbed disposal of surfactant material from type II pneumocytes rather than that from storage material of type I pneumocyte.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chamlian A, Gulion JM, Benkoël L (1986) Ultrastructural and enzyme hitochemical study of liver in Niemann-Pick disease. Cell Mol Biol 32:273–282
Dumontel C, Girod C, Dijoud F, Dumez Y, Vanier MT (1993) Fetal Niemann-Pick disease type C: ultrastructural and lipid findings in liver and spleen. Virchows Arch [A] 422:253–259
Elleder M (1983) Niemann-Pick disease type C and sphingomyelinase deficiency. Differences in chemical and structural pathology. In: Elleder M, Jirásek A (eds) Niemann-Pick disease. Report on a symposium held in Hlava's Institute of Pathology, Prague 1982. Acta Univ Carolinae Med 29:259–267
Elleder M, Smid F, Hyniova H, Chihula J, Zeman J, Macek M (1984) Liver findings in Niemann-Pick disease type C. Histochem J 16:1147–1170
Fawcett DW (1986) A textbook of histology. 11th ed. W.B. Saunders, Philadelphia, pp 156–158; 384–391
Ham AN, Cormack DH (1979) Histology. 8th ed. J.B. Lippincott, Philadelphia, p 362
Higashi Y, Pentchev PG, Murayama S, Suzuki K (1991) Pathology of Niemann-Pick type C: studies of murine mutants. In: Ikuta F (ed) Neuropathology in brain research. Elsevier, Amsterdam, pp 85–102
Higashi Y, Murayama S, Pentchev PG, Suzuki K (1993) Cerebellar degeneration in the Niemann-Pick type C mouse. Acta Neuropathol [Berl] 85:175–184
Jobe AH, Jacobs HC (1984) Catabolism of pulmonary surfactant. In: Robertson B, Van Golde LMG, Batenburg JJ (eds) Pulmonary surfactant. Elsevier, Amsterdam, 271–293
Manabe T (1979) Freeze-fracture study of alveolar lining layer in adult rat lungs. J Ultrastruct Res 69:86–97
Palmer M, Green WR, Maumenee IH, Valle DL, Singer HS, Morton SJ et al. (1985) Niemann-Pick disease-type C. Ocular histopathologic and electron microscopic studies. Arch Ophthalmol 103:817–822
Pentchev PG, Gal AE, Booth AD, Omodeo-Sale F, Fouks J, Neumeyer BA et al. (1980) A lysosomal storage disorder in mice characterized by a dual deficiency of sphingomyelinase and glucocerebrosidase. Biochim Biophys Acta 619:669–679
Pentchev PG, Comly ME, Kruth HS, Patel S, Proestel M, Weintroub H (1986) The cholesterol storage disorder of the mutant BALB/c mouse. A primary genetic lesion closely linked to defective esterification of exogenously derived cholesterol and its relationship to human type C Niemann-Pick disease. J Biol Chem 261:2772–2777
Pentchev PG, Vanier MT, Suzuki K, Pattson MC (in press) Niemann-Pick disease type C: A cellular cholesterol lipidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. 7th edn. McGraw-Hill, New York
Shio H, Fowler S, Bhuvaneswaran C, Morris MD (1982) Lysosome lipid strage disorder in NCTR-BALB/c mice. II. Morphologic and cytochemical studies. Am J Patol 108:150–159
Skikne MI, Prinsoloo I, Webster I (1972) Electron microscopy of lung in Niemann-Pick disease. J Pathol 106:119–122
Sokol J, Blachette-Mackie EJ, Kruth HS, Dwyer NK, Amende LM, Butler JD et al. (1988) Type C Niemann-Pick disease. Lysosomal accumulation and defective intracellular mobilization of low density lipoprotein cholesterol. J Biol Chem 263:3411–3417
Spence NW, Callahan JW (1989) Sphingomyelin-cholesterol lipidoses: the Niemann-Pick group of diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease II. 6th edn. McGraw-Hill, New York, pp 1655–1676
Tanaka J, Nakamura H, Miyawaki S (1988) Cerebellar involvement in murine sphingomyelinosis: a new model of Niemann-Pick disease. J Neuropathol Exp Neurol 47:291–300
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Manabe, T., Yamane, T., Higashi, T. et al. Ultrastructural changes in the lung in Niemann-Pick type C mouse. Vichows Archiv A Pathol Anat 427, 77–83 (1995). https://doi.org/10.1007/BF00203741
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00203741