• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Aug 1986; 78(2): 482–493.
PMCID: PMC423585

Immunolocalization of elastase in human emphysematous lungs.

Abstract

The current working hypothesis concerning the pathogenesis of human pulmonary emphysema proposes that neutrophils migrate through the alveolar interstitium and degranulate, releasing proteolytic enzymes into the interstitium. These enzymes, in particular elastase, can bind to and degrade interstitial elastin. This report describes an immunohistochemical, ultrastructural technique that utilizes polyclonal antibodies to localize neutrophil elastase in human lungs. Using both the immunoperoxidase and the immunogold methods on thin, embedded sections of surgically resected human emphysematous lung tissue, elastase was localized in neutrophils in the lung interstitium and extracellularly in association with interstitial elastic fibers in human lungs that showed local emphysema of varying severity. Quantitative morphometric data were obtained from the lungs of eight patients undergoing lobectomy for removal of pulmonary carcinomas. Patients had preoperative forced expiratory volume (FEV1)% levels ranging from 55 to 77. There was a correlation between a quantitative measure of the local distribution of neutrophil elastase in contact with alveolar interstitial elastin and the local presence of emphysematous change as determined by mean linear intercept of the various histologic sections. These data support the validity of the "protease-protease inhibitor balance hypothesis" as an explanation of the pathogenesis of human pulmonary emphysema.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (5.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Janoff A. Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis. Am Rev Respir Dis. 1985 Aug;132(2):417–433. [PubMed]
  • Gadek JE, Fells GA, Zimmerman RL, Rennard SI, Crystal RG. Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema. J Clin Invest. 1981 Oct;68(4):889–898. [PMC free article] [PubMed]
  • Abrams WR, Cohen AB, Damiano VV, Eliraz A, Kimbel P, Meranze DR, Weinbaum G. A model of decreased functional alpha-1-proteinase inhibitor. Pulmonary pathology of dogs exposed to chloramine T. J Clin Invest. 1981 Nov;68(5):1132–1139. [PMC free article] [PubMed]
  • Marco V, Mass B, Meranze DR, Weinbaum G, Kimbel P. Induction of experimental emphysema in dogs using leukocyte homogenates. Am Rev Respir Dis. 1971 Oct;104(4):595–598. [PubMed]
  • Janoff A, Sloan B, Weinbaum G, Damiano V, Sandhaus RA, Elias J, Kimbel P. Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. Am Rev Respir Dis. 1977 Mar;115(3):461–478. [PubMed]
  • Senior RM, Tegner H, Kuhn C, Ohlsson K, Starcher BC, Pierce JA. The induction of pulmonary emphysema with human leukocyte elastase. Am Rev Respir Dis. 1977 Sep;116(3):469–475. [PubMed]
  • Sloan B, Abrams WR, Meranze DR, Kimbel P, Weinbaum G. Emphysema induced in vitro and in vivo in dogs by a purified elastase from homologous leukocytes. Am Rev Respir Dis. 1981 Sep;124(3):295–301. [PubMed]
  • Snider GL. The pathogenesis of emphysema--twenty years of progress. Am Rev Respir Dis. 1981 Sep;124(3):321–324. [PubMed]
  • McDowell EM, Trump BF. Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med. 1976 Aug;100(8):405–414. [PubMed]
  • Segal AW, Fortunato A, Herd T. A rapid single centrifugation step method for the separation of erythrocytes, granulocytes and mononuclear cells on continuous density gradients of Percoll. J Immunol Methods. 1980;32(3):209–214. [PubMed]
  • Watt SM, Burgess AW, Metcalf D. Isolation and surface labeling of murine polymorphonuclear neutrophils. J Cell Physiol. 1979 Jul;100(1):1–21. [PubMed]
  • Damiano VV, Sandler A, Abrams WR, Meranze DR, Cohen AB, Kimbel P, Weinbaum G. Electron and light microscopic studies of the lungs of chloramine-T treated dogs. Bull Eur Physiopathol Respir. 1980;16 (Suppl):141–156. [PubMed]
  • Baugh RJ, Travis J. Human leukocyte granule elastase: rapid isolation and characterization. Biochemistry. 1976 Feb 24;15(4):836–841. [PubMed]
  • Delshammar M, Ohlsson K. Isolation and partial characterization of elastase from dog granulocytes. Eur J Biochem. 1976 Oct 1;69(1):125–131. [PubMed]
  • Kucich U, Abrams WR, James HL. Solid-phase immunoassay of dog neutrophil elastase. Anal Biochem. 1980 Dec;109(2):403–409. [PubMed]
  • Bainton DF, Ullyot JL, Farquhar MG. The development of neutrophilic polymorphonuclear leukocytes in human bone marrow. J Exp Med. 1971 Oct 1;134(4):907–934. [PMC free article] [PubMed]
  • Baggiolini M, Bretz U, Dewald B, Feigenson ME. The polymorphonuclear leukocyte. Agents Actions. 1978 Jan;8(1-2):3–10. [PubMed]
  • Graham RC, Jr, Karnovsky MJ. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. [PubMed]
  • Travis J, Salvesen GS. Human plasma proteinase inhibitors. Annu Rev Biochem. 1983;52:655–709. [PubMed]
  • Cosio MG, Hale KA, Niewoehner DE. Morphologic and morphometric effects of prolonged cigarette smoking on the small airways. Am Rev Respir Dis. 1980 Aug;122(2):265–221. [PubMed]
  • Wright JL, Lawson LM, Pare PD, Wiggs BJ, Kennedy S, Hogg JC. Morphology of peripheral airways in current smokers and ex-smokers. Am Rev Respir Dis. 1983 Apr;127(4):474–477. [PubMed]
  • Hoidal JR, Niewoehner DE. Lung phagocyte recruitment and metabolic alterations induced by cigarette smoke in humans and in hamsters. Am Rev Respir Dis. 1982 Sep;126(3):548–552. [PubMed]
  • Hunninghake GW, Crystal RG. Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers. Am Rev Respir Dis. 1983 Nov;128(5):833–838. [PubMed]
  • Stone PJ, Calore JD, Snider GL, Franzblau C. The dose-dependent fate of enzymatically active and inactivated tritiated methylated pancreatic elastase administered intratracheally in the hamster. Am Rev Respir Dis. 1979 Sep;120(3):577–587. [PubMed]
  • Sandhaus RA, Janoff A. Elastase-induced emphysema: retention of instilled proteinase in the rat. Am Rev Respir Dis. 1982 Nov;126(5):914–920. [PubMed]
  • Campbell EJ, Senior RM, McDonald JA, Cox DL. Proteolysis by neutrophils. Relative importance of cell-substrate contact and oxidative inactivation of proteinase inhibitors in vitro. J Clin Invest. 1982 Oct;70(4):845–852. [PMC free article] [PubMed]
  • Weiss SJ, Regiani S. Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor. Cooperative use of lysosomal proteinases and oxygen metabolites. J Clin Invest. 1984 May;73(5):1297–1303. [PMC free article] [PubMed]
  • Reilly CF, Travis J. The degradation of human lung elastin by neutrophil proteinases. Biochim Biophys Acta. 1980 Jan 24;621(1):147–157. [PubMed]
  • Kuhn C, 3rd, Engleman W, Chraplyvy M, Starcher BC. Degradation of elastin in experimental elastase-induced emphysema measured by a radioimmunoassay for desmosine. Exp Lung Res. 1983 Sep;5(2):115–123. [PubMed]
  • Powers JC. Synthetic elastase inhibitors: prospects for use in the treatment of emphysema. Am Rev Respir Dis. 1983 Feb;127(2):S54–S58. [PubMed]
  • Campbell EJ, White RR, Senior RM, Rodriguez RJ, Kuhn C. Receptor-mediated binding and internalization of leukocyte elastase by alveolar macrophages in vitro. J Clin Invest. 1979 Sep;64(3):824–833. [PMC free article] [PubMed]
  • Campbell EJ. Human leukocyte elastase, cathepsin G, and lactoferrin: family of neutrophil granule glycoproteins that bind to an alveolar macrophage receptor. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6941–6945. [PMC free article] [PubMed]
  • McGowan SE, Arbeit RD, Stone PJ, Snider GL. A comparison of the binding and fate of internalized neutrophil elastase in human monocytes and alveolar macrophages. Am Rev Respir Dis. 1983 Oct;128(4):688–694. [PubMed]
  • 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. [PubMed]

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

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...