RESEARCH PAPER
Mouse model of hypersensitivity pneumonitis after inhalation exposure to different microbial antigens associated with organic dusts
 
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1
Institute of Rural Health, Lublin, Poland
2
Department of Pathology and Diagnostic, Section of Pathological Anatomy, University of Verona, Verona, Italy
3
Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Brussels, Belgium
4
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland
CORRESPONDING AUTHOR
Marta Lemieszek   

Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
 
Ann Agric Environ Med. 2011;18(1):159–168
KEYWORDS
ABSTRACT
The aim of this study was to reproduce in laboratory conditions hypersensitivity pneumonitis (HP) pathogenesis in a new animal model predictive of the human response, and to select the microbial antigen associated with organic dust that exerts the strongest pathogenic effect on the respiratory organ. To achieve this goal, mice of the strain C57BL/6J prone to fibrosis were exposed for 1 hour daily up to 28 days to the inhalation of aerosols of each of the 5 microbial components of organic dusts whose conjunction with the occurrence of HP has been confirmed by numerous authors: Pantoea agglomerans saline extract (SE), P. agglomerans microvesicle-bound endotoxin, Saccharopolyspora rectivirgula SE, Aspergillus fumigatus SE, saline extract of dust from a grain sample overgrown with S. rectivirgula and Thermoactinomyces vulgaris, and a saline solvent (PBS) was used as a control. Exposure of the animals to organic dust components was conducted using a novel inhalation challenge set. Lung samples were collected from untreated mice and from mice exposed for 7 and 28 days, and examined by digitalized histopathology and biochemistry for the presence of inflammatory changes and fibrosis. P. agglomerans SE appeared to be the sole antigen which evoked a statistically significant fibrosis and a significant increase of hydroxyproline in the lungs of mice exposed for 28 days to this extract, both compared to the mice untreated and to those exposed to the solvent. P. agglomerans SE also evoked the strongest and statistically significant inflammatory response in the lungs of the mice, both after 7 and 28 days of exposure. After 7 days, significant inflammatory changes were also found in mice exposed to A. fumigatus SE, and after 28 days in mice exposed to all antigens. In conclusion, our results allow us to define a useful animal model of HP which can be a supplement for now commony used bleomycin model. This model should comprise: present set of instruments for inhalation, mice of the line C57BL/6J and the saline extract of P. agglomerans as the antigen. For a better understanding of the presented results, a detailed study covering immunological investigations, focused on the mechanism of antigen action, are needed.
 
REFERENCES (41)
1.
Ávila R, Lacey J: The role of Penicillium frequentans in suberosis (respiratory disease in workers in the cork industry). Clin Allergy 1974, 4, 109–117.
 
2.
Bhakdi S: Microbial toxins. Wien Klin Wochenschr 1998, 110, 660–668.
 
3.
Biondi PA, Chiesa LM, Storelli MR, Renon P: A new procedure for the specifi c high-performance liquid chromatographic determination of hydroxyproline. J Chromatogr Sci 1997, 35, 509–512.
 
4.
Blank C, Luz A, Bendigs S, Erdmann A, Wagner H, Heeg K: Superantigen and endotoxin synergize in the induction of lethal shock. Eur J Immunol 1997, 27, 825–833.
 
5.
Bourke SJ: Longitudinal course of extrinsic allergic alveolitis in pigeon breeders. Thorax 1989, 44, 415–419.
 
6.
Burrell R: Immunotoxic reactions in the agricultural environment. Ann Agric Environ Med 1995, 2, 11–20.
 
7.
Burrell R, Ye SH: Toxic risks from inhalation of bacterial endotoxin. Br J Ind Med 1990, 47, 688–691.
 
8.
Campbell JM: Acute symptoms following work with hay. Brit Med J 1932, 2, 1143–1147.
 
9.
De Haller R, Suter F (Eds): Aspergillosis and Farmer’s Lung in Man and Animal. Hans Huber Publishers, Bern 1974.
 
10.
DeLucca AJ II, Godshall MA, Palmgren MS: Gram-negative bacterial endotoxins in grain elevator dusts. Am Ind Hyg Assoc J 1984, 45, 336–339.
 
11.
DeLucca AJ II, Palmgren MS: Mesophilic microorganisms and endotoxin levels on developing cotton plants. Am Ind Hyg Assoc J 1986, 47, 437–442.
 
12.
Denis M, Cormier Y, Fournier M, Tardif J, Laviolette M: Tumor necrosis factor plays an essential role in determining hypersensitivity pneumonitis in a mouse model. Am J Respir Cell Mol Biol 1991, 5, 477-483.
 
13.
De Vuyst P, Dalphin JC: Occupational interstitial lung diseases. Rev Prat 2007, 57, 2266–2276 (in French).
 
14.
Dileto CL, Travis EL: Fibroblast radiosensitivity in vitro and lung fi brosis in vivo: comparison between a fi brosis-prone and fi brosisresistant mouse strain. Radiat Res 1996, 146(1), 61–67.
 
15.
DiSalvo AF (Ed.): Occupational Mycoses. Lee & Febiger, Philadelphia 1983.
 
16.
Dutkiewicz J: Studies on endotoxins of Erwinia herbicola and their biological activity. Zbl Bakt Hyg I Abt Orig A 1976, 236, 487–508.
 
17.
Dutkiewicz J: Exposure to dust-borne bacteria in agriculture. I. Environmental studies. Arch Environ Health 1978, 33, 250–259.
 
18.
Dutkiewicz J: Exposure to dust – borne bacteria in agriculture. II. Immunological survey. Arch Environ Health 1978, 33, 260–270.
 
19.
Dutkiewicz J, Kuś L: Effect of an inhalation of exogenous bacterial allergen Erwinia herbicola on number of free cells in lungs. Immunol Pol 1983, 8, 37–45 (in Polish).
 
20.
Dutkiewicz J, Minárik L, Skórska C, Krysińska-Traczyk E, Votrubová V, Mayer M: Microbiological and clinical analysis of disease cases after occupational exposure to beech chips in the factory of cellulose. Pneum Pol 1984, 52, 57–69 (in Polish).
 
21.
Dutkiewicz J, Kuś L, Dutkiewicz E, Warren CPW: Hypersensitivity pneumonitis in grain farmers due to sensitization to Erwinia herbicola. Ann Allergy 1985, 54, 65–68.
 
22.
Dutkiewicz J: Microbial hazards in plants processing grain and herbs. In: Rylander R, Peterson Y, Donham KJ (Eds): Health Effects of Organic Dusts in the Farm Environment. Proceedings of an International Workshop held in Skokloster, Sweden, April 23–25, 1985. Am J Ind Med 1986, 10, 300–302.
 
23.
Dutkiewicz J: Bacteria in farming environment. Eur J Respir Dis 1987, 71, 71–88.
 
24.
Dutkiewicz J, Tucker J, Woodfork K, Burrell R: The identifi cation of extracellular endotoxin molecules by immunoelectron microscopy. In: Jacobs RR, Wakelyn PJ (Eds): Cotton Dust. Proceedings of the 13th Cotton Dust Research Conference, Nashville, Tennessee, 5–6 January 1989, 111–114.
 
25.
National Cotton Council, Memphis, TN 1989. 25. Dutkiewicz J, Tucker J, Burrell R, Olenchock SA, Schwegler-Berry D, Keller III GE, Ochalska B, Kaczmarski F, Skórska C: Ultrastructure of the endotoxin produced by Gram-negative bacteria associated with organic dusts. System Appl Microbiol 1992,.
 
26.
474–485. 26. Dutkiewicz J, Krysińska-Traczyk E, Skórska C, Sitkowska J, Prażmo Z, Urbanowicz B: Exposure of agricultural workers to airborne microorganisms and endotoxin during handling of various vegetable products. Aerobiologia 2000, 16, 193–198.
 
27.
Dutkiewicz J, Skórska C, Burrell R, Szuster-Ciesielska A, Sitkowska J: Immunostimulative effects of repeated inhalation exposure to microvesicle-bound endotoxin of Pantoea agglomerans. Ann Agric Environ Med 2005, 12, 289–294.
 
28.
Edwards JH: The isolation of antigens associated with farmer’s lung. Clin Exp Immunol 1972, 11, 341–355.
 
29.
Emanuel DA, Wenzel FJ, Bowerman CI, Lawton BR: Farmer’s lung. Clinical, pathologic and immunologic study of twenty-four patients. Am J Med 1964, 37, 392–401.
 
30.
Fink JN, Hensley GT, Barboriak JJ: An animal model of a hypersensitivity pneumonitis. J Allergy 1970, 46, 156–161.
 
31.
Fink JN: Hypersensitivity pneumonities. J Allergy Clin Immunol 1984, 74, 1–9.
 
32.
Fink J: Hypersensitivity pneumonitis. In: Merchant JA, Boehlecke BA, Taylor G, Pickett-Harner M (Eds): Occupational Respiratory Diseases, 481-500. DHHS (NIOSH) Publ no. 86–102, US Department of Health and Human Services, Washington 1986.
 
33.
Fogelmark B, Sjöstrand M, Rylander R: Pulmonary infl ammation induced by repeated inhalations of β(1,3)-D-glucan and endotoxin. Int J Exp Path 1994, 75, 85–90.
 
34.
Golec M, Skórska C, Mackiewicz B, Dutkiewicz J: Immunologic reactivity to work-related airborne allergens in people occupationally exposed to dust from herbs. Ann Agric Environ Med 2004, 11, 121–127.
 
35.
Golec M, Skórska C, Lemieszek M, Dutkiewicz J: A novel inhalation challenge set to study animal model of allergic alveolitis. Ann Agric Environ Med 2009, 16, 173–175.
 
36.
Góra A, Mackiewicz B, Krawczyk P, Golec M, Skórska C, Sitkowska J, Cholewa G, Larsson L, Jarosz M, Wójcik-Fatla A, Dutkiewicz J: Occupational exposure to organic dust, microorganisms, endotoxin and peptidoglycan among plants processing workers in Poland. Ann Agric Environ Med 2009, 16, 143–150.
 
37.
Kirsten D, Nowak D, Kanzow G, Magnussen H: Hypersensitivity pneumonitis in a gardener: persistent bronchoalveolar lavage lymphocytosis despite antigen avoidance. Ann Agric Environ Med 1994, 1, 77–79.
 
38.
Kryda MJ, Emanuel DA: Farmer’s lung disease and other hypersensitivity pneumonitides. In: Sarosi GA, Davies SF (Eds): Fungal Diseases of the Lung. Grune & Stratton, Inc. New York 1986.
 
39.
Krysińska-Traczyk E, Skórska C, Prażmo Z, Sitkowska J, Cholewa G, Dutkiewicz J: Exposure to airborne microorganisms, dust and endotoxin during fl ax scutching on farms. Ann Agric Environ Med 2004, 11, 309–317.
 
40.
Kuś L, Wójtowicz Z, Brajerski W, Dutkiewicz J, Umiński J, Dutkiewicz E, Szukiewicz Z: Farmer’s lung (description of clinical cases). Gruźlica 1973, 41, 881–888 (in Polish).
 
41.
Kuś L: Allergic alveolitis after exposure to antigens occurring in grain dust in the light of the own clinical and experimental studies. Med Wiejska 1980, 15, 73–80 (in Polish).
 
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