Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
권호 표지

The Effects of Air-borne Particulate Matters on the Alveolar Macrophages for the TNF-α and IL-1β Secretion

미세분진이 흰쥐의 폐포대식세포에서 TNF-α와 IL-1β의 형성에 미치는 효과

  • Received : 2005.12.13
  • Accepted : 2006.05.02
  • Published : 2006.05.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: PM is known to induce various pulmonary diseases, including asthma, cancer, fibrosis and chronic bronchitis. Despite the epidemiological evidence the pathogenesis of PM-related pulmonary diseases is unclear. Methods: This study examined the effects of PM exposure on the secretion of $TNF-{\alpha}$ and $IL-1{\beta}$ in the cultured alveolar macrophages. The cultured primary alveolar macrophages were treated with the medium, PM ($5{\sim}20{\mu}g/cm^2$), LPS (5ng/ml), and PM with LPS for 24h and 48h respectively. ELISA was used to assay the secreted $TNF-{\alpha}$ and $IL-{\beta}$ in the culture medium. Western blotting was used to identify and determine the level of proteins isolated from the culture cells. The cells cultured in the $Lab-Tek^{(R)}$ chamber slides were stained with immunocytochemical stains. Results: PM induced $TNF-{\alpha}$ and $IL-1{\beta}$ secretion in the culturing alveolar macrophages, collected from the SPF and inflammatory rats. However, the effects were only dose-dependent in the inflammatory macrophages. When the cells were co-treated with PM and LPS, there was a significant synergistic effect compared with the LPS in the both cell types. Conclusion: PM might be play an important role in the induction and/or potentiation of various lung diseases by oversecretion of $TNF-{\alpha}$ and $IL-1{\beta}$.

연구 배경: 대도시의 대기오염은 점차 악화되어 시민의 건강을 위협하고, 심 폐 질환의 발병률과 이 로 인한 사망률을 증가시키고 있다. 서울시 도로가의 PM이 $TNF-{\alpha}$와 $IL-1{\beta}$의 생성에 직접적으로 어떠한 영향을 미치는지와 PM의 노출이 LPS의 $TNF-{\alpha}$와 $IL-1{\beta}$의 생성효과에는 어떠한 영향을 미치는지를 평가하고자 하였다. 방 법: 폐렴이 있는 흰쥐와 SPF 흰쥐의 폐포대식세포 각각에 PM을 농도별로 처리하여 분비되는 $TNF-{\alpha}$와 $IL-1{\beta}$의 농도를 측정하였다. 측정 방법으로는 western blot, ELISA 및 세포면역화학염색법을 이용하였다. 또한 동일 PM 농도에서 배양시간을 달리하여 위와 같이 측정하였다. 결 과: SPF인 흰쥐에서 분리된 페포대식세포에 PM을 단독으로 투여하였을 때 대조군에 비해서 $TNF-{\alpha}$와 $IL-1{\beta}$의 생성도가 모든 투여군에서 유의하게 증가하였으나, 투여용량의 증가에 따른 유의성은 없었다. 그러나 염증성인 쥐에서 분리된 폐포대식세포에서는 모든 투여군에서 대조군에 비하여 통계학적으로 유의하게 증가하였으며, PM 투여농도의 증가에 따른 생성량도 유의하게 증가하였다. 결 론: PM을 장기간 혹은 일정 농도 이상으로 흡입할 경우 폐포대식세포의 $TNF-{\alpha}$와 $IL-1{\beta}$의 분비에 영향을 미쳐 새로운 폐질환을 유발할 수 있다. 그러므로 기존에 염증성 폐질환이나 기관지천식이 있는 환자가 미세먼지를 흡입할 경우에는 $TNF-{\alpha}$와 $IL-1{\beta}$의 생성에 커다란 영향을 미쳐 호흡기 질환을 더욱 악화시킬 가능성이 있을 것으로 추정된다.

Keywords

References

  1. Harre ES, Price PD, Ayrey RB, Toop LJ, Martin IR, Town GI. Respiratory effects of air populution in chronic obstructive pulmonary disease: a three-month prospective study. Thorax 1997;52:1040-4 https://doi.org/10.1136/thx.52.12.1040
  2. Lebowitz MD. Epidemiological studies of the respiratory effects of air pollution. Eur Respir J 1996;9:1029-54 https://doi.org/10.1183/09031936.96.09051029
  3. Pope CA 3rd, Dockery DW, Spengler JD, Raizenne ME. Respiratory health and PM10 pollution: a daily time series analysis. Am Rev Respir Dis 1991;144:668-74 https://doi.org/10.1164/ajrccm/144.3_Pt_1.668
  4. Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Health effects of outdoor air pollution: part 2. Am J Respir Crit Care Med 1996;153:477-98 https://doi.org/10.1164/ajrccm.153.2.8564086
  5. Dockery DW, Pope CA 3rd. Acute respiratory effects of particulate air pollution. Annu Rev Public Health 1994;15:107-32 https://doi.org/10.1146/annurev.pu.15.050194.000543
  6. Pope CA 3rd, Kanner RE. Acute effects of PM10 pollution on pulmonary function of smokers with mild to moderate COPD. Am Rev Respir Dis 1993;147:1336-40 https://doi.org/10.1164/ajrccm/147.6_Pt_1.1336
  7. Emanuel MB. Hay fever, a post industrial revolution epidemic: a history of its growth during the 19th century. Clin Allergy 1988;18:295-304 https://doi.org/10.1111/j.1365-2222.1988.tb02872.x
  8. Abbey DE, Hwang BL, Burchette RJ, Vancuren T, Mills PK. Estimated long-term ambient concentrations of PM10 and development of respiratory symptoms in a nonsmoking population. Arch Environ Health 1995;50:139-52 https://doi.org/10.1080/00039896.1995.9940891
  9. Dusseldorp A, Kruize H, Brunekreef B, Hofschreuder P, de Meer G, van Oudvorst AB. Associations of PM10 and airbone iron with respiratory health of adults living near a steel factory. Am J Respir Crit Care Med 1995;152:1932-9 https://doi.org/10.1164/ajrccm.152.6.8520758
  10. Fels AO, Cohn ZA. The alveolar macrophage. J Appl Physiol 1986;60:353-69 https://doi.org/10.1152/jappl.1986.60.2.353
  11. Tracey KJ, Cerami A. Metabolic responses to cachectin/TNF. Ann N Y Acad Sci 1990;587:325-31 https://doi.org/10.1111/j.1749-6632.1990.tb00173.x
  12. Beutler B, Grau GE. Tumor necrosis factor in the pathogenesis of infectious diseases. Crit Care Med 1993;21:S423-35 https://doi.org/10.1097/00003246-199310001-00002
  13. Briscoe DM, Cotran RS, Pober JS. Effect of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo: correlation with CD3+T cell infiltrataion. J Immunol 1992;149:2954-60
  14. Gamber JR, Harlan JM, Klebanoff SJ, Vadas MA. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc Natl Acad Sci U S A 1985;82:8667-71 https://doi.org/10.1073/pnas.82.24.8667
  15. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy of immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993;119:1198-208 https://doi.org/10.7326/0003-4819-119-12-199312150-00007
  16. Tracy KJ, Fong Y, Hesse DG, Manogue KR, lee AT, Kuo GC, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock dmuring lethal bacteraemia. Nature 1987;330:662-4 https://doi.org/10.1038/330662a0
  17. Manel DN, Moore RN, Mergenhagen SE. Macrophages as a sourse of tumoricidal activity (tumor necrotizing factor). Infect Immun 1980;30:523-30
  18. Kim KA, Lee DW, Lim Y, Yun IG. Effect of asbestos on fibroblast proliferation of rat. Korean J Occup Environ Med 1996;8:392-402
  19. Lim Y, Kim KA, Kim HN, Lee DW, Cho WS, Yun IG. Cytotoxicity and apoptosis by silica, asbestos and man-made mineral fibers. Korean J Occup Environ Med 1997;9:641-9
  20. Lim Y, Kim KA, Yun IG. The measurement of IL-1, 8, TNF for the diagnosis of pneumoconiosis. Korean J Occup Environ Med 1997;9:17-25
  21. Lim Y, Kim SH, Cho YJ, Kim KA, Oh MW, Lee KH. Silica-inducced oxygen radical ge1neration in alveolar macrophage. Ind Health 1997;35:380-7 https://doi.org/10.2486/indhealth.35.380
  22. Vanhee D, Gosset P, Marquette CH, Wallaert B, Lafitte JJ, Gosselin B, et al. Secretion and mRNA expression of TNF alpha and IL-6 in the lungs of pneumocaniosis patients. Am J Respir Crit Med 1995;152:298-306 https://doi.org/10.1164/ajrccm.152.1.7599837