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Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients With Mustard Gas-Induced Pulmonary Fibrosis

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Abstract

Objective

Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of IL-5, RANTES (CCL5) and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF).

Patients

Fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group.

Intervention

Pulmonary function tests, tests for DLCO, computed tomography scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases.

Results

Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03; r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too.

Conclusion

A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis due to SM gas inhalation has been demonstrated, suggesting that these C–C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.

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References

  1. Aasted A, Darre E, Wulf HC. Mustard gas: clinical, toxicological and mutagenic aspects based on modern experience. Ann Plast Surg 1987;19:330–33.

    Article  PubMed  CAS  Google Scholar 

  2. Calvet JH, Jarreau HP, Levame M, Lorino H, d’Ortho MP, Harf A, et al. Acute and chronic effects of sulfur mustard intoxication in the guinea pig. J Appl Physiol 1994;76:681–8.

    PubMed  CAS  Google Scholar 

  3. Papirmeister B, Gross CL, Meier HL, Petrali JP, Johnson JB. Molecular basis for mustard-induced vesication. Fundam Appl Toxicol 1985;5:S134–49.

    Article  PubMed  CAS  Google Scholar 

  4. Anderson DR, Byers SL, Vesely KR. Treatment of sulfur mustard (HD)-induced lung injuries. J Appl Toxicol 2000;20:S129.

    Article  PubMed  CAS  Google Scholar 

  5. Emad A, Rezaian GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. Chest 1997;112:734–8.

    PubMed  CAS  Google Scholar 

  6. Emad A, Rezaian GR. Characteristics of bronchoalveolar lavage fluid in patients with sulfur mustard gas-induced asthma or chronic bronchitis. Am J Med 1999;106:689–90.

    Article  Google Scholar 

  7. Emad A, Rezaian GR. Immunoglobulins and cellular constituents of the BAL fluid of patients with sulfur mustard gas-Induced pulmonary fibrosis. Chest 1999;115:1346–51.

    Article  PubMed  CAS  Google Scholar 

  8. Emad A, Rezaian GR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. Chest 1997;112:734–8.

    PubMed  CAS  Google Scholar 

  9. Czarnobilska E, Obtulowicz K. Eosinophil in allergic and non-allergic inflammation. Przegl Lek 2005;62(12):1484–7.

    PubMed  Google Scholar 

  10. Worthylake RA, Burridge K. Leukocyte transendothelial migration: orchestrating the underlying molecular machinery. Curr Opin Cell Biol 2001;31:569–77.

    Article  Google Scholar 

  11. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. Am J Respir Crit Care Med 2000;161:646–64.

    Google Scholar 

  12. Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. General considerations for lung function testing. Eur Respir J 2005;26:153–61.

    Article  PubMed  CAS  Google Scholar 

  13. Cotes JE, Chinn DJ, Quanjer PhH, Roca J, Yernault J-C. Standardization of the measurement of transfer factor (diffusing capacity). Report working party, Standardization of lung function tests, European Community for steel and coal. Official Statement of the European Respiratory Society. Eur Respir J 1993:41–52.

  14. Pellegrino R, Viegi G, Brusasco V, Crapo RO, Burgos F, Casaburi R, et al. Interpretative strategies for lung function tests. Eur Respir J 2005;26:948–68.

    Article  PubMed  CAS  Google Scholar 

  15. Agostini C, Meneghin A, Semenzato G. T-lymphocytes and cytokines in sarcoidosis. Curr Opin Pulm Med 2002;8:435–40 (Sep, review).

    Article  PubMed  Google Scholar 

  16. Emad A, Emad Y. Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis. Res Med 2007;101:786–92.

    Article  Google Scholar 

  17. Emad A, Emad Y. Levels of cytokines in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J Interferon Cytokine Res 2007;27:38–43.

    Article  PubMed  CAS  Google Scholar 

  18. Gross TJ, Hunninghake GW. Idiopathic pulmonary fibrosis. N Engl J Med 2001;345:517.

    Article  PubMed  CAS  Google Scholar 

  19. Moser B, Willimann K. Chemokines: role in inflammation and immune surveillance. Ann Rheum Dis 2004;63:84–9.

    Article  CAS  Google Scholar 

  20. Anonymous. Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups. The BAL Cooperative Group Steering Committee. Am Rev Respir Dis 1990;141:S169–S202.

    Google Scholar 

  21. Manzo A, Caporali R, Montecucco C, Pitzalis C. Role of chemokines and chemokine receptors in regulating specific leukocyte trafficking in the immune/inflammatory response. Clin Exp Rheumatol 2003;21:501–8.

    PubMed  CAS  Google Scholar 

  22. Olson TS, Ley K. Chemokines and chemokine receptors in leukocyte trafficking. Am J Physiol Regul Integr Comp Physiol. 2002;283:R7–28.

    PubMed  CAS  Google Scholar 

  23. Ahn YT, Huang B, McPherson L, Clayberger C, Krensky AM. Dynamic interplay of transcriptional machinery and chromatin regulates “late” expression of the chemokine RANTES in T lymphocytes. Mol Cell Biol 2007;27:253–66.

    Article  PubMed  CAS  Google Scholar 

  24. Chiba T, Kamada Y, Saito N, Oyamada H, Ueki S, Kobayashi Y, et al. RANTES and eotaxin enhance CD11b and CD18 expression on eosinophils from allergic patients with eosinophilia in the application of whole blood flow cytometry analysis. Int Arch Allergy Immunol 2005;137 Suppl 1:12–6.

    Article  PubMed  CAS  Google Scholar 

  25. Costa GG, Silva RM, Franco-Penteado CF, Antunes E, Ferreira HH. Interactions between eotaxin and interleukin-5 in the chemotaxis of primed and non-primed human eosinophils. Eur J Pharmacol 2007; 566:200–5.

    Article  PubMed  CAS  Google Scholar 

  26. Itakura A, Kikuchi Y, Kouro T, Ikutani M, Takaki S, Askenase PW, et al. Interleukin 5 plays an essential role in elicitation of contact sensitivity through dual effects on eosinophils and B-1 cells. Int Arch Allergy Immunol 2006;140 Suppl 1:8–16.

    Article  PubMed  CAS  Google Scholar 

  27. Umetsu DT. Revising the immunological theories of asthma and allergy. Lancet 2005;365(9454):98–100 (Jan 8–14).

    Article  PubMed  Google Scholar 

  28. Kaatz M, Berod L, Czech W, Idzko M, Lagadari M, Bauer A, et al. Interleukin-5, interleukin-3 and granulocyte–macrophage colony-stimulating factor prime actin-polymerization in human eosinophils: a study with hypodense and normodense eosinophils from patients with atopic dermatitis. Int J Mol Med 2004;14 (6):1055–60.

    PubMed  CAS  Google Scholar 

  29. Fulkerson PC, Fischetti CA, McBride ML, Hassman LM, Hogan SP, Rothenberg ME. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci USA 2006;103(44):16418–23.

    Article  PubMed  CAS  Google Scholar 

  30. Lampinen M, Rak S, Venge P. The role of interleukin-5, interleukin-8 and RANTES in the chemotactic attraction of eosinophils to the allergic lung. Clin Exp Allergy 1999;29:314–22.

    Article  PubMed  CAS  Google Scholar 

  31. Ebisawa M, Yamada T, Bickel C, Klunk D, Schleimer RP. Eosinophil transendothelial migration induced by cytokines. III. Effect of the chemokine RANTES. J Immunol 1994;153:2153–60.

    PubMed  CAS  Google Scholar 

  32. Alam R, Stafford S, Forsythe P, Grant GA. RANTES is a chemotactic and activating factor for eosinophils. J Immunol 1993;150:3442–7.

    PubMed  CAS  Google Scholar 

  33. Moore BB, Coffey MJ, Christensen P, Sitterding S, Ngan R, Wilke CA, et al. GM-CSF regulates bleomycin-induced pulmonary fibrosis via a prostaglandin-dependent mechanism. J Immunol 2000;165:4032–9.

    PubMed  CAS  Google Scholar 

  34. Hao H, Cohen DA, Jennings CD, Bryson JS, Kaplan AM. Bleomycin-induced pulmonary fibrosis is independent of eosinophils. J Leukoc Biol 2000;68:515–21.

    PubMed  CAS  Google Scholar 

  35. Dombrowicz D, Capron M. Eosinophils, allergy and parasites. Curr Opin Immunol 2001;13:716.

    Article  PubMed  CAS  Google Scholar 

  36. Boomars KA, Wagenaar SS, Mulder PG, van Velzen-Blad H, van den Bosch JM. Relationship between cells obtained by bronchoalveolar lavage and survival in idiopathic pulmonary fibrosis. Thorax 1995;50:1087–92.

    Article  PubMed  CAS  Google Scholar 

  37. Zhang K, Gharaee-Kermani M, Jones ML, Warren JS, Phan SH. Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced pulmonary fibrosis. J Immunol 1994;153:4733–41.

    PubMed  CAS  Google Scholar 

  38. Zhang K, Flanders KC, Phan SH. Cellular localization of transforming growth factor-beta expression in bleomycin-induced pulmonary fibrosis. Am J Pathol 1995;147:352–61.

    PubMed  CAS  Google Scholar 

  39. Zhang K, Gharaee Kermani M, McGarry B, Remick D, Phan SH. TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis. J Immunol 1997;158:954–9.

    PubMed  CAS  Google Scholar 

  40. Coker RK, Laurent GJ, Shahzeidi S, Lympany PA, du Bois RM, Jeffery PK, et al. Transforming growth factors-β[1], -β[2], and -β[3] stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis. Am J Pathol 1997;150:981–91.

    PubMed  CAS  Google Scholar 

  41. Rochester CL, Ackerman SJ, Zheng T, Elias JA. Eosinophil-fibroblast interactions. Granule major basic protein interacts with IL-1 and transforming growth factor-beta in the stimulation of lung fibroblast IL-6-type cytokine production. J Immunol 1996;156:4449–56.

    PubMed  CAS  Google Scholar 

  42. Shlopov BV, Hasty KA. Collagenase expression by normal human eosinophils. J Leukoc Biol 1998;63:451–5.

    PubMed  CAS  Google Scholar 

  43. Cantin A, Fells G, Given JT, Nichols WK, Crystal RG. Sensitivity of the lung to oxidants: cells of the lower respiratory tract are relatively deficient in scavengers of H202. Am Rev Respir Dis 1993;127:163.

    Google Scholar 

  44. Kodama N, Yamaguchi E, Hizawa N, Furuya K, Kojima J, Oguri M, et al. Expression of RANTES by bronchoalveolar lavage cells in nonsmoking patients with interstitial lung diseases. Am J Respir Cell Mol Biol 1998;18:526–31.

    PubMed  CAS  Google Scholar 

  45. Walker C, Bauer W, Braun RK, Menz G, Braun P, Schwarz F, et al. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med 1994;150:1038–48.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Pulmonary Diseases, Shiraz University of Medical Sciences, P.O. Box 71345-1674, Shiraz, Iran

    Ali Emad

  2. Shiraz University, Shiraz, Iran

    Yasaman Emad

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Correspondence to Ali Emad.

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Emad, A., Emad, Y. Relationship Between Eosinophilia and Levels of Chemokines (CCL5 and CCL11) and IL-5 in Bronchoalveolar Lavage Fluid of Patients With Mustard Gas-Induced Pulmonary Fibrosis. J Clin Immunol 27, 605–612 (2007). https://doi.org/10.1007/s10875-007-9114-y

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