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Mechanisms of occupational asthma: Not all allergens are equal

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Abstract

Asthma is a heterogeneous lung disorder characterized by airway obstruction, inflammation and eosinophil infiltration into the lung. Both genetics and environmental factors influence the expression of asthma, and not all asthma is the result of a specific immune response to allergen. Numerous asthma phenotypes have been described, including occupational asthma, and therapeutic strategies for asthma control are similar regardless of phenotype. We hypothesized that mechanistic pathways leading to asthma symptoms in the effector phase of the disorder differ with the inciting allergen. Since route of allergen exposure can influence mechanistic pathways, mice were sensitized by identical routes with a high molecular weight occupational allergen ovalbumin and a low molecular weight occupational allergen trimellitic anhydride (TMA). Different statistical methods with varying selection criteria resulted in identification of similar candidate genes. Array data are intended to provide candidate genes for hypothesis generation and further experimentation. Continued studies focused on genes showing minimal changes in the TMA-induced model but with clear up-regulation in the ovalbumin model. Two of these genes, arginase 1 and eotaxin 1 are the focus of continuing investigations in mouse models of asthma regarding differences in mechanistic pathways depending on the allergen. Microarray data from the ovalbumin and TMA model of asthma were also compared to previous data usingAspergillus as allergen to identify putative asthma ‘signature genes’, i.e. genes up-regulated with all 3 allergens. Array studies provide candidate genes to identify common mechanistic pathways in the effector phase, as well as mechanistic pathways unique to individual allergens.

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References

  1. Global Initiative for Asthma: Global Strategy for Asthma Management and Prevention (GINA). Bethesda: National Institutes of Health, National Heart Lung and Blood Institute: 2002. Report No 02-3659.

  2. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–813.

    Article  PubMed  CAS  Google Scholar 

  3. Lancet editorial. A plea to abandon asthma as a disease concept. Lancet. 2006;368:705.

  4. Morley J. Inflammation and asthma therapy: a false dawn. Pulm Pharmacol Ther. 2006;19:200–204.

    Article  PubMed  CAS  Google Scholar 

  5. Jenkins HA, Cherniack R, Szefler SJ, Covr R, Gelfand EW, Spahn JD. A comparison of the clinical characteristics of children and adults with severe asthma. Chest. 2003;124:1318–1324.

    Article  PubMed  Google Scholar 

  6. Bernstein IL, Bernstein DI, Chan-Yeung M, Malo JL. Definition and classification of asthma in the workplace. In: Bernstein IL, Chan-Yeung M, Malo JL, Bernstein DI editors. Asthma in the Workplace, 3rd ed. New York: Taylor & Francis; 2006. p. 1–8.

    Google Scholar 

  7. Smith AB, Bernstein DI, London MA, Gallagher J, Ornella GA, Gelletly SK, et al. Evaluation of occupational asthma from airborne egg protein exposure in multiple settings. Chest. 1990;98:398–404.

    Article  PubMed  CAS  Google Scholar 

  8. Boeniger MF, Lummus ZL, Biagini RE, Bernstein DI, Swanson MC, Reed C, et al. Exposure to protein aeroallergens in egg processing facilities. Appl Occup Environ Hyg. 2001;16:660–670.

    Article  PubMed  CAS  Google Scholar 

  9. Escudero C, Quirce S, Fernandez-Nieto M, de Miguel J, Cuesta J, Sastre J. Egg white proteins as inhalant allergens associated with baker’s asthma. Allergy. 2003;58:616–620.

    Article  PubMed  CAS  Google Scholar 

  10. Wisnewski AV, Redlich CA, Mapp CE, Bernstein DI. Polyisocyanates and their prepolymers. In: Bernstein IL, Chan-Yeung M, Malo JL, Bernstein DI editors. Asthma in the Workplace, 3rd ed. New York: Taylor & Francis: 2006. p. 481–504.

    Google Scholar 

  11. Zeiss CR, Patterson R, Pruzansky JJ, Miller MM, Rosenberg M, Levitz D. Trimellitic anhydride-induced airway syndromes: Clinical and immunologic studies. J Allergy Clin Immunol. 1977;60:96–103.

    Article  PubMed  CAS  Google Scholar 

  12. Karp CL, Grupe A, Schadt E, Ewart SL, Keane-Moore M, Cuomo PJ, et al. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nature Immunol. 2000;1:221–226.

    Article  CAS  Google Scholar 

  13. Zimmermann N, King NE, Laporte J, Yang M, Mishra A, Pope SM, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Investigation. 2003;111:1863–1874.

    CAS  Google Scholar 

  14. Yang M, Rangasamy D, Matthaei KI, Frew AJ, Zimmermann N, Mahalingam S, et al. Inhibition of arginase I activity by RNA interference attenuates IL-13-induced airways hyper-responsiveness. J Immunol. 2006;177:5595–5603.

    PubMed  CAS  Google Scholar 

  15. King NE, Zimmermann N, Pope SM, Fulkerson PC, Nikolaidis NM, Mishra A, et al. Expression and regulation of a disintegrin and metalloproteinase (ADAM) 8 in experimental asthma. Am J Respir Cell Mol Biol. 2004;31:257–265.

    Article  PubMed  CAS  Google Scholar 

  16. Nikolaidis NM, Zimmermann N, King NE, Mishra A, Pope SM, Finkelman FD, et al. Trefoil factor-2 is an allergen induced gene regulated by Th2 cytokines and STAT6 in the lung. Am J Respir Cell Mol Biol. 2003;29:458–464.

    Article  PubMed  CAS  Google Scholar 

  17. Zimmermann N, Doepker MP, Witte DP, Stringer KF, Fulkerson PC, Pope SM, et al. Expression and regulation of small proline-rich protein 2 in allergic inflammation. Am J Respir Cell Mol Biol. 2005;32:428–435.

    Article  PubMed  CAS  Google Scholar 

  18. Zimmermann N, Mishra A, King NE, Fulerson PC, Doepker MP, Nikolaidis NM, et al. Transcript signatures in experimental asthma: Identification of STAT6-dependent and-independent pathways. J Immunol. 2004;172:1815–1824.

    PubMed  CAS  Google Scholar 

  19. Regal JF. Immunologic effector mechanisms in animal models of occupational asthma. J Immunotoxicology. 2004;1:25–38.

    Article  CAS  Google Scholar 

  20. Brewer JP, Kisselgof AB, Martin TR. Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice. Am J Respir Crit Care Med. 1999;160:1150–1156.

    PubMed  CAS  Google Scholar 

  21. Saito H, Abe J, Matsumoto K. Allergy-related genes in microarray: An update review. J Allergy Clin Immunol. 2005;116:56–59.

    Article  PubMed  CAS  Google Scholar 

  22. Greene AL, Rutherford MS, Regal RR, Flickinger GH, Hendrickson JA, Giulivi C, et al. Arginase activity differs with allergen in the effector phase of ovalbumin-versus trimellitic anhydride-induced asthma. Toxicol Sci. 2005;88: 420–433.

    Article  PubMed  CAS  Google Scholar 

  23. Cui X, Churchill G. A. How many mice and how many arrays? Replication in mouse cDNA microarray experiments. In: Johnson KF, Lin SM editors. Methods of Microarray Data Analysis III. Norwell, MA: Kluwer Academic Publishers; 2003. p. 139–154.

    Google Scholar 

  24. Storey JD, Tibshirani R. Statistical significance for genome-wide studies. Proc Natl Acad Sci USA. 2003;100:9440–9445.

    Article  PubMed  CAS  Google Scholar 

  25. Irizarry RA, Bolstad BM, Collin F, Cope LM, Hobbs B, Speed TP. Summaries of Affymetrix genechip probe level data. Nucleic Acids Res. 2003;31:e15.

    Article  CAS  Google Scholar 

  26. Smyth GK. Linear Models and Empirical Bayes Methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology. 2004;3:Issue 1, article 3. Available at:http://www.bepress.com/sagmb/vol3/iss1/art3.

  27. Malerba G, Pignatti PF. A review of asthma genetics: gene expression studies and recent candidates. J Appl Genet. 2005; 46:93–104.

    PubMed  Google Scholar 

  28. Rolph MS, Sisavanh M, Liu SM, Mackay CR. Clues to asthma pathogenesis from microarray expression studies. Pharmacol & Therapeutics. 2006;109:284–294.

    Article  CAS  Google Scholar 

  29. Hansel NN, Diette GB. Gene expression profiling in human asthma. Proc Am Thorac Soc. 2007;4:32–36.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jean F. Regal.

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Regal, J.F., Greene, A.L. & Regal, R.R. Mechanisms of occupational asthma: Not all allergens are equal. Environ Health Prev Med 12, 165–171 (2007). https://doi.org/10.1007/BF02897986

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  • DOI: https://doi.org/10.1007/BF02897986

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