Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 May;87(5):1828–1834. doi: 10.1172/JCI115204

Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.

S D Shapiro 1, S K Endicott 1, M A Province 1, J A Pierce 1, E J Campbell 1
PMCID: PMC295305  PMID: 2022748

Abstract

Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related 14C. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14C were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; Kasp (1.76 x 10(-3) yr(-1) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of "aging lung" is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin.

Full text

PDF
1828

Selected References

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

  1. Abrams W. R., Fein A. M., Kucich U., Kueppers F., Yamada H., Kuzmowycz T., Morgan L., Lippmann M., Goldberg S. K., Weinbaum G. Proteinase inhibitory function in inflammatory lung disease. I. Acute bacterial pneumonia. Am Rev Respir Dis. 1984 May;129(5):735–741. doi: 10.1164/arrd.1984.129.5.735. [DOI] [PubMed] [Google Scholar]
  2. BROECKER W. S., SCHULERT A., OLSON E. A. Bomb carbon-14 in human beings. Science. 1959 Aug 7;130(3371):331–332. doi: 10.1126/science.130.3371.331-a. [DOI] [PubMed] [Google Scholar]
  3. Bada J. L., Luyendyk B. P., Maynard J. B. Marine sediments: dating by the racemization of amino acids. Science. 1970 Nov 13;170(3959):730–732. doi: 10.1126/science.170.3959.730. [DOI] [PubMed] [Google Scholar]
  4. Bada J. L., Protsch R. Racemization reaction of aspartic Acid and its use in dating fossil bones. Proc Natl Acad Sci U S A. 1973 May;70(5):1331–1334. doi: 10.1073/pnas.70.5.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bada J. L., Schroeder R. A., Carter G. F. New evidence for the antiquity of man in North America deduced from aspartic acid racemization. Science. 1974 May 17;184(4138):791–793. doi: 10.1126/science.184.4138.791. [DOI] [PubMed] [Google Scholar]
  6. Bada J. L., Schroeder R. A., Protsch R., Berger R. Concordance of collagen-based radiocarbon and aspartic-acid racemization ages. Proc Natl Acad Sci U S A. 1974 Mar;71(3):914–917. doi: 10.1073/pnas.71.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bailey E., Farmer P. B., Lamb J. H. The enantiomer as internal standard for the quantitation of the alkylated amino acid S-methyl-L-cysteine in haemoglobin by gas chromatography-chemical ionisation mass spectrometry with single ion detection. J Chromatogr. 1980 Nov 21;200:145–152. doi: 10.1016/s0021-9673(00)84925-0. [DOI] [PubMed] [Google Scholar]
  8. Brooks A. S., Hare P. E., Kokis J. E., Miller G. H., Ernst R. D., Wendorf F. Dating pleistocene archeological sites by protein diagenesis in ostrich eggshell. Science. 1990 Apr 6;248(4951):60–64. doi: 10.1126/science.248.4951.60. [DOI] [PubMed] [Google Scholar]
  9. Cleary E. G., Gibson M. A. Elastin-associated microfibrils and microfibrillar proteins. Int Rev Connect Tissue Res. 1983;10:97–209. doi: 10.1016/b978-0-12-363710-9.50009-5. [DOI] [PubMed] [Google Scholar]
  10. Darnule T. V., McKee M., Darnule A. T., Turino G. M., Mandl I. Solid-phase radioimmunoassay for estimation of elastin peptides in human sera. Anal Biochem. 1982 May 15;122(2):302–307. doi: 10.1016/0003-2697(82)90286-x. [DOI] [PubMed] [Google Scholar]
  11. Davies S. F., Offord K. P., Brown M. G., Campe H., Niewoehner D. Urine desmosine is unrelated to cigarette smoking or to spirometric function. Am Rev Respir Dis. 1983 Sep;128(3):473–475. doi: 10.1164/arrd.1983.128.3.473. [DOI] [PubMed] [Google Scholar]
  12. Dubick M. A., Rucker R. B., Cross C. E., Last J. A. Elastin metabolism in rodent lung. Biochim Biophys Acta. 1981 Feb 5;672(3):303–306. doi: 10.1016/0304-4165(81)90297-x. [DOI] [PubMed] [Google Scholar]
  13. Elmore D., Phillips F. M. Accelerator mass spectrometry for measurement of long-lived radioisotopes. Science. 1987 May 1;236(4801):543–550. doi: 10.1126/science.236.4801.543. [DOI] [PubMed] [Google Scholar]
  14. Fazio M. J., Olsen D. R., Kuivaniemi H., Chu M. L., Davidson J. M., Rosenbloom J., Uitto J. Isolation and characterization of human elastin cDNAs, and age-associated variation in elastin gene expression in cultured skin fibroblasts. Lab Invest. 1988 Mar;58(3):270–277. [PubMed] [Google Scholar]
  15. Frank H., Nicholson G. J., Bayer E. Enantiomer labelling, a method for the quantitative analysis of amino acids. J Chromatogr. 1978 Dec 21;167:187–196. doi: 10.1016/s0021-9673(00)91157-9. [DOI] [PubMed] [Google Scholar]
  16. Frank H., Rettenmeier A., Weicker H., Nicholson G. J., Bayer E. A new gas chromatographic method for determination of amino acid levels in human serum. Clin Chim Acta. 1980 Aug 4;105(2):201–211. doi: 10.1016/0009-8981(80)90462-3. [DOI] [PubMed] [Google Scholar]
  17. Gibson M. A., Kumaratilake J. S., Cleary E. G. The protein components of the 12-nanometer microfibrils of elastic and nonelastic tissues. J Biol Chem. 1989 Mar 15;264(8):4590–4598. [PubMed] [Google Scholar]
  18. Gunja-Smith Z., Boucek R. J. Desmosines in human urine. Amounts in early development and in Marfan's syndrome. Biochem J. 1981 Mar 1;193(3):915–918. doi: 10.1042/bj1930915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Harkness D. D. Further investigations of the transfer of bomb 14 C to man. Nature. 1972 Dec 1;240(5379):302–303. doi: 10.1038/240302a0. [DOI] [PubMed] [Google Scholar]
  20. Heinrikson R. L., Meredith S. C. Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate. Anal Biochem. 1984 Jan;136(1):65–74. doi: 10.1016/0003-2697(84)90307-5. [DOI] [PubMed] [Google Scholar]
  21. Helfman P. M., Bada J. L. Aspartic acid racemisation in dentine as a measure of ageing. Nature. 1976 Jul 22;262(5566):279–281. doi: 10.1038/262279b0. [DOI] [PubMed] [Google Scholar]
  22. Helfman P. M., Bada J. L. Aspartic acid racemization in tooth enamel from living humans. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2891–2894. doi: 10.1073/pnas.72.8.2891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Indik Z., Yeh H., Ornstein-Goldstein N., Sheppard P., Anderson N., Rosenbloom J. C., Peltonen L., Rosenbloom J. Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5680–5684. doi: 10.1073/pnas.84.16.5680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Janoff A. Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis. Am Rev Respir Dis. 1985 Aug;132(2):417–433. doi: 10.1164/arrd.1985.132.2.417. [DOI] [PubMed] [Google Scholar]
  25. John R., Thomas J. Chemical compositions of elastins isolated from aortas and pulmonary tissues of humans of different ages. Biochem J. 1972 Mar;127(1):261–269. doi: 10.1042/bj1270261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Johnson D. A., Carter-Hamm B., Dralle W. M. Inactivation of human bronchial mucosal proteinase inhibitor by Pseudomonas aeruginosa elastase. Am Rev Respir Dis. 1982 Dec;126(6):1070–1073. doi: 10.1164/arrd.1982.126.6.1070. [DOI] [PubMed] [Google Scholar]
  27. Kucich U., Christner P., Lippmann M., Fein A., Goldberg A., Kimbel P., Weinbaum G., Rosenbloom J. Immunologic measurement of elastin-derived peptides in human serum. Am Rev Respir Dis. 1983 Feb;127(2):S28–S30. doi: 10.1164/arrd.1983.127.2P2.S28. [DOI] [PubMed] [Google Scholar]
  28. Kucich U., Christner P., Lippmann M., Kimbel P., Williams G., Rosenbloom J., Weinbaum G. Utilization of a peroxidase antiperoxidase complex in an enzyme-linked immunosorbent assay of elastin-derived peptides in human plasma. Am Rev Respir Dis. 1985 May;131(5):709–713. doi: 10.1164/arrd.1985.131.5.709. [DOI] [PubMed] [Google Scholar]
  29. LIBBY W. F., BERGER R., MEAD J. F., ALEXANDER G. V., ROSS J. F. REPLACEMENT RATES FOR HUMAN TISSUE FROM ATMOSPHERIC RADIOCARBON. Science. 1964 Nov 27;146(3648):1170–1172. doi: 10.1126/science.146.3648.1170. [DOI] [PubMed] [Google Scholar]
  30. Lefevre M., Rucker R. B. Aorta elastin turnover in normal and hypercholesterolemic Japanese quail. Biochim Biophys Acta. 1980 Jul 15;630(4):519–529. doi: 10.1016/0304-4165(80)90006-9. [DOI] [PubMed] [Google Scholar]
  31. Man E. H., Sandhouse M. E., Burg J., Fisher G. H. Accumulation of D-aspartic acid with age in the human brain. Science. 1983 Jun 24;220(4604):1407–1408. doi: 10.1126/science.6857259. [DOI] [PubMed] [Google Scholar]
  32. Masters P. M., Bada J. L., Zigler J. S., Jr Aspartic acid racemisation in the human lens during ageing and in cataract formation. Nature. 1977 Jul 7;268(5615):71–73. doi: 10.1038/268071a0. [DOI] [PubMed] [Google Scholar]
  33. Mecham R. P., Hinek A., Cleary E. G., Kucich U., Lee S. J., Rosenbloom J. Development of immunoreagents to ciliary zonules that react with protein components of elastic fiber microfibrils and with elastin-producing cells. Biochem Biophys Res Commun. 1988 Mar 15;151(2):822–826. doi: 10.1016/s0006-291x(88)80355-3. [DOI] [PubMed] [Google Scholar]
  34. Niewoehner D. E. Cigarette smoking, lung inflammation, and the development of emphysema. J Lab Clin Med. 1988 Jan;111(1):15–27. [PubMed] [Google Scholar]
  35. Nydal R., Lövseth K., Syrstad O. Bomb 14 C in the human population. Nature. 1971 Aug 6;232(5310):418–421. doi: 10.1038/232418a0. [DOI] [PubMed] [Google Scholar]
  36. Paz M. A., Keith D. A., Traverso H. P., Gallop P. M. Isolation, purification, and cross-linking profiles of elastin from lung and aorta. Biochemistry. 1976 Nov 2;15(22):4912–4918. doi: 10.1021/bi00667a025. [DOI] [PubMed] [Google Scholar]
  37. Pelham F., Wewers M., Crystal R., Buist A. S., Janoff A. Urinary excretion of desmosine (elastin cross-links) in subjects with PiZZ alpha-1-antitrypsin deficiency, a phenotype associated with hereditary predisposition to pulmonary emphysema. Am Rev Respir Dis. 1985 Oct;132(4):821–823. doi: 10.1164/arrd.1985.132.4.821. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Rasmussen B. L., Bruenger E., Sandberg L. B. A new method for purification of mature elastin. Anal Biochem. 1975 Mar;64(1):255–259. doi: 10.1016/0003-2697(75)90426-1. [DOI] [PubMed] [Google Scholar]
  40. Reeck G. R., Fisher L. A statistical analysis of the amino acid compositions of proteins. Int J Pept Protein Res. 1973;5(2):109–117. doi: 10.1111/j.1399-3011.1973.tb02325.x. [DOI] [PubMed] [Google Scholar]
  41. Richmond V. Lung parenchymal elastin isolated by non-degradative means. Biochim Biophys Acta. 1974 Jun 7;351(2):173–177. doi: 10.1016/0005-2795(74)90178-0. [DOI] [PubMed] [Google Scholar]
  42. Rosenbloom J. Elastin: relation of protein and gene structure to disease. Lab Invest. 1984 Dec;51(6):605–623. [PubMed] [Google Scholar]
  43. Sandberg L. B., Soskel N. T., Leslie J. G. Elastin structure, biosynthesis, and relation to disease states. N Engl J Med. 1981 Mar 5;304(10):566–579. doi: 10.1056/NEJM198103053041004. [DOI] [PubMed] [Google Scholar]
  44. Soskel N. T., Sandburg L. B. A comparison of six methods of extracting elastin residue from hamster lungs. Exp Lung Res. 1983 Feb;4(2):109–119. doi: 10.3109/01902148309055008. [DOI] [PubMed] [Google Scholar]
  45. Starcher B. C. Elastin and the lung. Thorax. 1986 Aug;41(8):577–585. doi: 10.1136/thx.41.8.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Starcher B. C., Galione M. J. Purification and comparison of elastins from different animal species. Anal Biochem. 1976 Aug;74(2):441–447. doi: 10.1016/0003-2697(76)90224-4. [DOI] [PubMed] [Google Scholar]
  47. Starcher B. C., Goldstein R. A. Studies on the absorption of desmosine and isodesmosine. J Lab Clin Med. 1979 Dec;94(6):848–852. [PubMed] [Google Scholar]
  48. Stenhouse M. J., Baxter M. S. Bomb 14C as a biological tracer. Nature. 1977 Jun 30;267(5614):828–832. doi: 10.1038/267828a0. [DOI] [PubMed] [Google Scholar]
  49. The definition of emphysema. Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases workshop. Am Rev Respir Dis. 1985 Jul;132(1):182–185. doi: 10.1164/arrd.1985.132.1.182. [DOI] [PubMed] [Google Scholar]
  50. Thurlbeck W. M., Dunnill M. S., Hartung W., Heard B. E., Heppleston A. G., Ryder R. C. A comparison of three methods of measuring emphysema. Hum Pathol. 1970 Jun;1(2):215–226. doi: 10.1016/s0046-8177(70)80035-1. [DOI] [PubMed] [Google Scholar]
  51. WALFORD R. L., CARTER P. K., SCHNEIDER R. B. STABILITY OF LABELED AORTIC ELASTIC TISSUE WITH AGE AND PREGNANCY IN THE RAT. Arch Pathol. 1964 Jul;78:43–45. [PubMed] [Google Scholar]
  52. Wehmiller J., Hare P. E. Racemization of amino acids in marine sediments. Science. 1971 Sep 3;173(4000):907–911. doi: 10.1126/science.173.4000.907. [DOI] [PubMed] [Google Scholar]
  53. Wewers M. Pathogenesis of emphysema. Assessment of basic science concepts through clinical investigation. Chest. 1989 Jan;95(1):190–195. doi: 10.1378/chest.95.1.190. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES