Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1978 Jun;91(3):413–432.

The lung of the copper-deficient rat. A model for developmental pulmonary emphysema.

B L O'Dell, K H Kilburn, W N McKenzie, R J Thurston
PMCID: PMC2018314  PMID: 207187

Abstract

Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a "washed out" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema.

Full text

PDF
430

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Fisk D. E., Kuhn C. Emphysema-like changes in the lungs of the blotchy mouse. Am Rev Respir Dis. 1976 Jun;113(6):787–797. doi: 10.1164/arrd.1976.113.6.787. [DOI] [PubMed] [Google Scholar]
  2. GROSS P., PFITZER E. A., TOLKER E., BABYAK M. A., KASCHAK M. EXPERIMENTAL EMPHYSEMA: ITS PRODUCTION WITH PAPAIN IN NORMAL AND SILICOTIC RATS. Arch Environ Health. 1965 Jul;11:50–58. doi: 10.1080/00039896.1965.10664169. [DOI] [PubMed] [Google Scholar]
  3. HEPPLESTON A. G. The pathology of honeycomb lung. Thorax. 1956 Jun;11(2):77–93. doi: 10.1136/thx.11.2.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hance A. J., Crystal R. G. The connective tissue of lung. Am Rev Respir Dis. 1975 Nov;112(5):657–711. doi: 10.1164/arrd.1975.112.5.657. [DOI] [PubMed] [Google Scholar]
  5. Harris E. D., Gonnerman W. A., Savage J. E., O'Dell B. L. Connective tissue amine oxidase. II. Purification and partial characterization of lysyl oxidase from chick aorta. Biochim Biophys Acta. 1974 Apr 25;341(2):332–344. doi: 10.1016/0005-2744(74)90226-5. [DOI] [PubMed] [Google Scholar]
  6. Henderson R., Hislop A., Reid L. New pathological findings in emphysema of childhood. 3. Unilateral congenital emphysema with hypoplasia--and compensatory emphysema of contralateral lung. Thorax. 1971 Mar;26(2):195–205. doi: 10.1136/thx.26.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hislop A., Reid L. New pathological findings in emphysema of childhood. 1. Polyalveolar lobe with emphysema. Thorax. 1970 Nov;25(6):682–690. doi: 10.1136/thx.25.6.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hoffman L., Mondshine R. B., Park S. S. Effect of DL-penicillamine on elastic properties of rat lung. J Appl Physiol. 1971 Apr;30(4):508–511. doi: 10.1152/jappl.1971.30.4.508. [DOI] [PubMed] [Google Scholar]
  9. Johanson W. G., Jr, Pierce A. K. Effects of elastase, collagenase, and papain on structure and function of rat lungs in vitro. J Clin Invest. 1972 Feb;51(2):288–293. doi: 10.1172/JCI106813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Johanson W. G., Jr, Reynolds R. C., Scott T. C., Pierce A. K. Connective tissue damage in emphysema. An electron microscopic study of papain-induced emphysema in rats. Am Rev Respir Dis. 1973 Apr;107(4):589–595. doi: 10.1164/arrd.1973.107.4.589. [DOI] [PubMed] [Google Scholar]
  11. Kaplan P. D., Kuhn C., Pierce J. A. The induction of emphysema with elastase. I. The evolution of the lesion and the influence of serum. J Lab Clin Med. 1973 Sep;82(3):349–356. [PubMed] [Google Scholar]
  12. Kilburn K. E. New clues for the emphysemas. Am J Med. 1975 May;58(5):591–600. doi: 10.1016/0002-9343(75)90495-7. [DOI] [PubMed] [Google Scholar]
  13. LANSING A. I., ROSENTHAL T. B., ALEX M., DEMPSEY E. W. The structure and chemical characterization of elastic fibers as revealed by elastase and by electron microscopy. Anat Rec. 1952 Dec;114(4):555–575. doi: 10.1002/ar.1091140404. [DOI] [PubMed] [Google Scholar]
  14. LOOSLI C. G., POTTER E. L. Pre- and postnatal development of the respiratory portion of the human lung with special reference to the elastic fibers. Am Rev Respir Dis. 1959 Jul;80(1 Pt 2):5–23. doi: 10.1164/arrd.1959.80.1P2.5. [DOI] [PubMed] [Google Scholar]
  15. MACLEOD W. M. Abnormal transradiancy of one lung. Thorax. 1954 Jun;9(2):147–153. doi: 10.1136/thx.9.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morgan R. F., O'Dell B. L. Effect of copper deficiency on the concentrations of catecholamines and related enzyme activities in the rat brain. J Neurochem. 1977 Jan;28(1):207–213. doi: 10.1111/j.1471-4159.1977.tb07728.x. [DOI] [PubMed] [Google Scholar]
  17. Murray G. F. Congenital lobar emphysema. Surg Gynecol Obstet. 1967 Mar;124(3):611–625. [PubMed] [Google Scholar]
  18. O'DELL B. L., HARDWICK B. C., REYNOLDS G., SAVAGE J. E. Connective tissue defect in the chick resulting from copper deficiency. Proc Soc Exp Biol Med. 1961 Nov;108:402–405. doi: 10.3181/00379727-108-26951. [DOI] [PubMed] [Google Scholar]
  19. Pierce J. A., Resnick H., Henry P. H. Collagen and elastin metabolism in the lungs, skin, and bones of adult rats. J Lab Clin Med. 1967 Mar;69(3):485–493. [PubMed] [Google Scholar]
  20. Pinnell S. R., Martin G. R. The cross-linking of collagen and elastin: enzymatic conversion of lysine in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone. Proc Natl Acad Sci U S A. 1968 Oct;61(2):708–716. doi: 10.1073/pnas.61.2.708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rowe D. W., McGoodwin E. B., Martin G. R., Grahn D. Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse. J Biol Chem. 1977 Feb 10;252(3):939–942. [PubMed] [Google Scholar]
  22. SHIELDS G. S., COULSON W. F., KIMBALL D. A., CARNES W. H., CARTWRIGHT G. E., WINTROBE M. M. Studies on copper metabolism. 32. Cardiovascular lesions in copper-deficient swine. Am J Pathol. 1962 Nov;41:603–621. [PMC free article] [PubMed] [Google Scholar]
  23. SWYER P. R., JAMES G. C. A case of unilateral pulmonary emphysema. Thorax. 1953 Jun;8(2):133–136. doi: 10.1136/thx.8.2.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Siegel R. C., Pinnell S. R., Martin G. R. Cross-linking of collagen and elastin. Properties of lysyl oxidase. Biochemistry. 1970 Nov 10;9(23):4486–4492. doi: 10.1021/bi00825a004. [DOI] [PubMed] [Google Scholar]
  25. Snider G. L., Hayes J. A., Korthy A. L., Lewis G. P. Centrilobular emphysema experimentally induced by cadmium chloride aerosol. Am Rev Respir Dis. 1973 Jul;108(1):40–48. doi: 10.1164/arrd.1973.108.1.40. [DOI] [PubMed] [Google Scholar]
  26. Stanley N. N., Alper R., Cunningham E. L., Cherniack N. S., Kefalides N. A. Effects of a molecular change in collagen on lung structure and mechanical function. J Clin Invest. 1975 Jun;55(6):1195–1201. doi: 10.1172/JCI108037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thurston R. J., Hess R. A., Kilburn K. H., McKenzie W. N. Ultrastructure of lungs fixed in inflation using a new osmium-fluorocarbon technique. J Ultrastruct Res. 1976 Jul;56(1):39–47. doi: 10.1016/s0022-5320(76)80139-6. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES