Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 2000 Jun;108(6):533–537. doi: 10.1289/ehp.00108533

Serum clara cell protein: a sensitive biomarker of increased lung epithelium permeability caused by ambient ozone.

F Broeckaert 1, K Arsalane 1, C Hermans 1, E Bergamaschi 1, A Brustolin 1, A Mutti 1, A Bernard 1
PMCID: PMC1638141  PMID: 10856027

Abstract

Ozone in ambient air may cause various effects on human health, including decreased lung function, asthma exacerbation, and even premature mortality. These effects have been evidenced using various clinical indicators that, although sensitive, do not specifically evaluate the O(3)-increased lung epithelium permeability. In the present study, we assessed the acute effects of ambient O(3) on the pulmonary epithelium by a new approach relying on the assay in serum of the lung-specific Clara cell protein (CC16 or CC10). We applied this test to cyclists who exercised for 2 hr during episodes of photochemical smog and found that O(3) induces an early leakage of lung Clara cell protein. The protein levels increased significantly into the serum from exposure levels as low as 0.060-0.084 ppm. Our findings, confirmed in mice exposed to the current U.S. National Ambient Air Quality Standards for O(3) (0.08 ppm for 8 hr) indicate that above the present natural background levels, there is almost no safety margin for the effects of ambient O(3) on airway permeability. The assay of CC16 in the serum represents a new sensitive noninvasive test allowing the detection of early effects of ambient O(3) on the lung epithelial barrier.

Full text

PDF
533

Images in this article

Selected References

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

  1. Abelson P. H. Proposed air pollutant standards. Science. 1997 Jul 4;277(5322):15–15. doi: 10.1126/science.277.5322.15. [DOI] [PubMed] [Google Scholar]
  2. Balmes J. R., Chen L. L., Scannell C., Tager I., Christian D., Hearne P. Q., Kelly T., Aris R. M. Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation. Am J Respir Crit Care Med. 1996 Mar;153(3):904–909. doi: 10.1164/ajrccm.153.3.8630571. [DOI] [PubMed] [Google Scholar]
  3. Barry B. E., Miller F. J., Crapo J. D. Effects of inhalation of 0.12 and 0.25 parts per million ozone on the proximal alveolar region of juvenile and adult rats. Lab Invest. 1985 Dec;53(6):692–704. [PubMed] [Google Scholar]
  4. Basha M. A., Gross K. B., Gwizdala C. J., Haidar A. H., Popovich J., Jr Bronchoalveolar lavage neutrophilia in asthmatic and healthy volunteers after controlled exposure to ozone and filtered purified air. Chest. 1994 Dec;106(6):1757–1765. doi: 10.1378/chest.106.6.1757. [DOI] [PubMed] [Google Scholar]
  5. Bernard A., Lauwerys R., Noel A., Vandeleene B., Lambert A. Determination by latex immunoassay of protein 1 in normal and pathological urine. Clin Chim Acta. 1991 Sep 30;201(3):231–245. doi: 10.1016/0009-8981(91)90374-l. [DOI] [PubMed] [Google Scholar]
  6. Bernard A., Marchandise F. X., Depelchin S., Lauwerys R., Sibille Y. Clara cell protein in serum and bronchoalveolar lavage. Eur Respir J. 1992 Nov;5(10):1231–1238. [PubMed] [Google Scholar]
  7. Broeckaert F., Buchet J. P., Huaux F., Lardot C., Lison D., Yager J. W. Reduction of the ex vivo production of tumor necrosis factor alpha by alveolar phagocytes after administration of coal fly ash and copper smelter dust. J Toxicol Environ Health. 1997 Jun 6;51(2):189–202. doi: 10.1080/00984109708984021. [DOI] [PubMed] [Google Scholar]
  8. Devlin R. B., McDonnell W. F., Mann R., Becker S., House D. E., Schreinemachers D., Koren H. S. Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung. Am J Respir Cell Mol Biol. 1991 Jan;4(1):72–81. doi: 10.1165/ajrcmb/4.1.72. [DOI] [PubMed] [Google Scholar]
  9. Gross K. B., White H. J., Sargent N. E. The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function. Toxicol Appl Pharmacol. 1991 Jun 15;109(2):336–351. doi: 10.1016/0041-008x(91)90180-m. [DOI] [PubMed] [Google Scholar]
  10. Gustafsson L. E., Cotgreave I. Ozone-induced toxicity in experimental animals and isolated cell systems. Scand J Work Environ Health. 1996;22 (Suppl 3):27–41. [PubMed] [Google Scholar]
  11. Halatek T., Hermans C., Broeckaert F., Wattiez R., Wiedig M., Toubeau G., Falmagne P., Bernard A. Quantification of Clara cell protein in rat and mouse biological fluids using a sensitive immunoassay. Eur Respir J. 1998 Mar;11(3):726–733. [PubMed] [Google Scholar]
  12. Harkema J. R., Plopper C. G., Hyde D. M., St George J. A., Wilson D. W., Dungworth D. L. Response of macaque bronchiolar epithelium to ambient concentrations of ozone. Am J Pathol. 1993 Sep;143(3):857–866. [PMC free article] [PubMed] [Google Scholar]
  13. Hermans C., Aly O., Nyberg B. I., Peterson C., Bernard A. Determinants of Clara cell protein (CC16) concentration in serum: a reassessment with two different immunoassays. Clin Chim Acta. 1998 Apr 27;272(2):101–110. doi: 10.1016/s0009-8981(98)00006-0. [DOI] [PubMed] [Google Scholar]
  14. Hermans C., Bernard A. Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med. 1999 Feb;159(2):646–678. doi: 10.1164/ajrccm.159.2.9806064. [DOI] [PubMed] [Google Scholar]
  15. Hermans C., Bernard A. Pneumoproteinaemia: a new perspective in the assessment of lung disorders. Eur Respir J. 1998 Apr;11(4):801–803. doi: 10.1183/09031936.98.11040801. [DOI] [PubMed] [Google Scholar]
  16. Kehrl H. R., Vincent L. M., Kowalsky R. J., Horstman D. H., O'Neil J. J., McCartney W. H., Bromberg P. A. Ozone exposure increases respiratory epithelial permeability in humans. Am Rev Respir Dis. 1987 May;135(5):1124–1128. doi: 10.1164/arrd.1987.135.5.1124. [DOI] [PubMed] [Google Scholar]
  17. Kleeberger S. R. Genetic susceptibility to ozone exposure. Toxicol Lett. 1995 Dec;82-83:295–300. doi: 10.1016/0378-4274(95)03564-8. [DOI] [PubMed] [Google Scholar]
  18. Newman D. J., Thakkar H., Edwards R. G., Wilkie M., White T., Grubb A. O., Price C. P. Serum cystatin C: a replacement for creatinine as a biochemical marker of GFR. Kidney Int Suppl. 1994 Nov;47:S20–S21. [PubMed] [Google Scholar]
  19. Schelegle E. S., Siefkin A. D., McDonald R. J. Time course of ozone-induced neutrophilia in normal humans. Am Rev Respir Dis. 1991 Jun;143(6):1353–1358. doi: 10.1164/ajrccm/143.6.1353. [DOI] [PubMed] [Google Scholar]
  20. Singh G., Katyal S. L. Clara cells and Clara cell 10 kD protein (CC10). Am J Respir Cell Mol Biol. 1997 Aug;17(2):141–143. doi: 10.1165/ajrcmb.17.2.f138. [DOI] [PubMed] [Google Scholar]
  21. Sundell J., Zuber A. Ozone and other photochemical oxidants in ambient and indoor air--properties, sources and concentrations. Scand J Work Environ Health. 1996;22 (Suppl 3):5–14. [PubMed] [Google Scholar]
  22. Young C., Bhalla D. K. Effects of ozone on the epithelial and inflammatory responses in the airways: role of tumor necrosis factor. J Toxicol Environ Health. 1995 Nov;46(3):329–342. doi: 10.1080/15287399509532039. [DOI] [PubMed] [Google Scholar]
  23. Young C., Bhalla D. K. Time course of permeability changes and PMN flux in rat trachea following O3 exposure. Fundam Appl Toxicol. 1992 Feb;18(2):175–180. doi: 10.1016/0272-0590(92)90043-h. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES