Solunum Hastalıklarında Deneysel Hayvan Modelleri

Year 2024, Volume: 26 Issue: S1, 47 - 54, 30.06.2024

Pınar Yıldız Gülhan

https://doi.org/10.18678/dtfd.1503737

Abstract

Akciğer hastalıkları, dünya genelinde morbidite ve mortalitenin önde gelen nedenlerindendir. Bu hastalıkların patogenezini anlamak ve yeni tedavi stratejileri geliştirmek için çeşitli hayvan modelleri kullanılmaktadır. Her model, astım ve kronik obstrüktif akciğer hastalığı (KOAH) gibi yaygın rahatsızlıklardan interstisyel akciğer hastalıklarına kadar akciğer sağlığının çok yönlü doğasını inceleme fırsatı sunar. Bu modeller normal fizyolojiyi ve hastalık patofizyolojisini anlamak ve hastalıklara yönelik potansiyel tedavileri test etmek için eşsiz bir fırsat sağlarken, tüm hayvan modellerinin doğası gereği sınırlamaları vardır. Bu derlemede, astım, KOAH ve pulmoner fibroz gibi yaygın akciğer hastalıklarının deneysel modellerine odaklanılmıştır. Her modelin avantajları, dezavantajları ve insan hastalığına translasyonel potansiyeli tartışılmaktadır. Astım modelleri arasında fareler, kobaylar ve Drosophila bulunurken, KOAH için elastazla indüklenen amfizem, sigara dumanına maruziyet ve genetik olarak değiştirilmiş fareler kullanılmaktadır. Pulmoner fibroz için ise bleomisin, adenoviral TGF-β1 vektörü, silika ve genetik olarak değiştirilmiş fare modelleri mevcuttur. Bu modeller, hastalık mekanizmalarına dair değerli bilgiler sağlamış ve yeni terapötik hedeflerin belirlenmesine yardımcı olmuştur. Bununla birlikte, her modelin insan hastalığını tam olarak yansıtmadığı ve her birinin kendine özgü avantajları ve sınırlamaları olduğu unutulmamalıdır. Bu nedenle, klinik öncesi çalışmalarda elde edilen bulguların insanlara uygulanabilirliğini dikkatlice değerlendirmek önemlidir.

Keywords

Akciğer hastalıkları, deney hayvanı, patogenez

Experimental Animal Models in Respiratory Diseases

Abstract

Respiratory diseases are among the leading causes of morbidity and mortality worldwide. Various animal models are used to understand the pathogenesis of these diseases and develop novel therapeutic strategies. Each model offers the opportunity to examine the multifaceted nature of pulmonary health, from common afflictions such as asthma and chronic obstructive pulmonary disease (COPD) to interstitial lung diseases. While these models provide a unique opportunity to understand normal physiology and disease pathophysiology and to test potential treatments for diseases, all animal models have inherent limitations. This review focuses on experimental models of common respiratory diseases such as asthma, COPD, and pulmonary fibrosis. The advantages, disadvantages, and translational potential to human disease of each model are discussed. Asthma models include mice, guinea pigs, and Drosophila, while elastase-induced emphysema, cigarette smoke exposure, and genetically modified mice are used for COPD. For pulmonary fibrosis, bleomycin, adenoviral TGF-β1 vector, silica, and genetically modified mice models are available. These models have provided valuable insights into disease mechanisms and aided in identifying new therapeutic targets. However, it is important to note that no single model fully recapitulates human disease, and each has its own unique advantages and limitations. Therefore, careful consideration of the translatability of findings from preclinical studies to humans is crucial.

Keywords

Experimental animal, lung diseases, pathogenesis

References

• Ware LB. Modeling human lung disease in animals. Am J Physiol Lung Cell Mol Physiol. 2008;294(2):L149-50.
• Shapiro SD. Animal models of asthma: Pro: Allergic avoidance of animal (model[s]) is not an option. Am J Respir Crit Care Med. 2006;174(11):1171-3.
• Fröhlich E. Animals in respiratory research. Int J Mol Sci. 2024;25(5):2903.
• Global Initiative for Asthma. Global strategy for asthma management and prevention. USA: Global Initiative for Asthma; 2016.
• Shinagawa K, Kojima M. Mouse model of airway remodeling: strain differences. Am J Respir Crit Care Med. 2003;168(8):959-67.
• Kumar RK, Herbert C, Yang M, Koskinen AM, McKenzie AN, Foster PS. Role of interleukin-13 in eosinophil accumulation and airway remodelling in a mouse model of chronic asthma. Clin Exp Allergy. 2002;32(7):1104-11.
• Aun MV, Bonamichi-Santos R, Arantes-Costa FM, Kalil J, Giavina-Bianchi P. Animal models of asthma: utility and limitations. J Asthma Allergy. 2017;10:293-301.
• Ehrhardt B, El-Merhie N, Kovacevic D, Schramm J, Bossen J, Roeder T, et al. Airway remodeling: The Drosophila model permits a purely epithelial perspective. Front Allergy. 2022;3:876673.
• Wagner C, Uliczka K, Bossen J, Niu X, Fink C, Thiedmann M, et al. Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways. Cell Rep. 2021;35(1):108956.
• Ressmeyer AR, Larsson AK, Vollmer E, Dahlèn SE, Uhlig S, Martin C. Characterisation of guinea pig precision-cut lung slices: comparison with human tissues. Eur Respir J. 2006;28(3):603-11.
• Woodrow JS, Sheats MK, Cooper B, Bayless R. Asthma: the use of animal models and their translational utility. Cells. 2023;12(7):1091.
• Yamaguchi T, Kohrogi H, Honda I, Kawano O, Sugimoto M, Araki S, et al. A novel leukotriene antagonist, ONO-1078, inhibits and reverses human bronchial contraction induced by leukotrienes C4 and D4 and antigen in vitro. Am Rev Respir Dis. 1992;146(4):923-9.
• Malo PE, Bell RL, Shaughnessy TK, Summers JB, Brooks DW, Carter GW. The 5-lipoxygenase inhibitory activity of zileuton in in vitro and in vivo models of antigen-induced airway anaphylaxis. Pulm Pharmacol. 1994;7(2):73-9.
• Adner M, Canning BJ, Meurs H, Ford W, Ramos Ramírez P, van den Berg MPM, et al. Back to the future: Re-establishing guinea pig in vivo asthma models. Clin Sci (Lond). 2020;134(11):1219-42.
• Skappak C, Ilarraza R, Wu YQ, Drake MG, Adamko DJ. Virus-induced asthma attack: The importance of allergic inflammation in response to viral antigen in an animal model of asthma. PLoS ONE. 2017;12(7):e0181425.
• Nials AT, Uddin S. Mouse models of allergic asthma: acute and chronic allergen challenge. Dis Model Mech. 2008;1(4-5):213-20.
• Zosky GR, Sly PD. Animal models of asthma. Clin Exp Allergy. 2007;37(7):973-88.
• Boyce JA, Austen KF. No audible wheezing: nuggets and conundrums from mouse asthma models. J Exp Med. 2005;201(12):1869-73.
• Kumar RK, Herbert C, Foster PS. The "classical" ovalbumin challenge model of asthma in mice. Curr Drug Targets. 2008;9(6):485-94.
• Kool M, Soullie T, van Nimwegen M, Willart MA, Muskens F, Jung S, et al. Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells. J Exp Med. 2008;205(4):869-82.
• Wagers S, Lundblad LK, Ekman M, Irvin CG, Bates JH. The allergic mouse model of asthma: normal smooth muscle in an abnormal lung? J Appl Physiol (1985). 2004;96(6):2019-27.
• Temelkovski J, Hogan SP, Shepherd DP, Foster PS, Kumar RK. An improved murine model of asthma: selective airway inflammation, epithelial lesions and increased methacholine responsiveness following chronic exposure to aerosolised allergen. Thorax. 1998;53(10):849-56.
• Fernandez-Rodriguez S, Ford WR, Broadley KJ, Kidd EJ. Establishing the phenotype in novel acute and chronic murine models of allergic asthma. Int Immunopharmacol. 2008;8(5):756-63.
• Jungsuwadee P, Benkovszky M, Dekan G, Stingl G, Epstein MM. Repeated aerosol allergen exposure suppresses inflammation in B-cell deficient mice with established allergic asthma. Int Arch Allergy Immunol. 2004;133(1):40-8.
• Ghorani V, Boskabady MH, Khazdair MR, Kianmeher M. Experimental animal models for COPD: a methodological review. Tob Induc Dis. 2017;15:25.
• Groneberg DA, Chung KF. Models of chronic obstructive pulmonary disease. Respir Res. 2004;5(1):18.
• Mortaz E, Adcock IA. Limitation of COPD studies in animal modeling. Tanaffos. 2012;11(3):7-8.
• Eltom S, Stevenson C, Birrell MA. Cigarette smoke exposure as a model of inflammation associated with COPD. Curr Protoc Pharmacol. 2013;5(5)64.
• Costa CH, Rufino R, Lapa E Silva JR. Inflammatory cells and their mediators in COPD pathogenesis. Rev Assoc Med Bras (1992). 2009;55(3):347-54. Portuguese.
• Liang GB, He ZH. Animal models of emphysema. Chin Med J (Engl). 2019;132(20):2465-75.
• Herget J, Palecek F, Cermáková M, Vízek M. Pulmonary hypertension in rats with papain emphysema. Respiration. 1979;38(4):204-12.
• Gülhan PY, Ekici MS, Niyaz M, Gülhan M, Erçin ME, Ekici A, et al. Therapeutic treatment with abdominal adipose mesenchymal cells does not prevent elastase-induced emphysema in rats. Turk Thorac J. 2020;21(1):14-20.
• Lucas SD, Gonçalves LM, Cardote TAF, Correia HF, Rui M, Guedes RC. Structure based virtual screening for discovery of novel human neutrophil elastase inhibitors. Med Chem Comm. 2012;3(10):1299-304.
• Wright JL, Churg A. Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig. Am Rev Respir Dis. 1990;142(6 Pt 1):1422-8.
• John G, Kohse K, Orasche J, Reda A, Schnelle-Kreis J, Zimmermann R, et al. The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models. Clin Sci (Lond). 2014;126(3):207-21.
• Shore S, Kobzik L, Long NC, Skornik W, Van Staden CJ, Boulet L, et al. Increased airway responsiveness to inhaled methacholine in a rat model of chronic bronchitis. Am J Respir Crit Care Med. 1995;151(6):1931-8.
• van der Strate BW, Postma DS, Brandsma CA, Melgert BN, Luinge MA, Geerlings M, et al. Cigarette smoke-induced emphysema: a role for the B cell? Am J Respir Crit Care Med. 2006;173(7):751-8.
• Churg A, Cosio M, Wright JL. Mechanisms of cigarette smoke-induced COPD: insights from animal models. Am J Physiol Lung Cell Mol Physiol. 2008;294(4):L612-31.
• Valenca SS, da Hora K, Castro P, Moraes VG, Carvalho L, Porto LC. Emphysema and metalloelastase expression in mouse lung induced by cigarette smoke. Toxicol Pathol. 2004;32(3):351-6.
• Wegmann M, Fehrenbach A, Heimann S, Fehrenbach H, Renz H, Garn H, et al. NO2-induced airway inflammation is associated with progressive airflow limitation and development of emphysema-like lesions in C57bl/6 mice. Exp Toxicol Pathol. 2005;56(6):341-50.
• Gupta V, Banyard A, Mullan A, Sriskantharajah S, Southworth T, Singh D. Characterization of the inflammatory response to inhaled lipopolysaccharide in mild to moderate chronic obstructive pulmonary disease. Br J Clin Pharmacol. 2015;79(5):767-76.
• Snider GL, Lucey EC, Faris B, Jung-Legg Y, Stone PJ, Franzblau C. Cadmium-chloride-induced air-space enlargement with interstitial pulmonary fibrosis is not associated with destruction of lung elastin. Implications for the pathogenesis of human emphysema. Am Rev Respir Dis. 1988;137(4):918-23.
• Keil M, Lungarella G, Cavarra E, van Even P, Martorana PA. A scanning electron microscopic investigation of genetic emphysema in tight-skin, pallid, and beige mice, three different C57 BL/6J mutants. Lab Invest. 1996;74(2):353-62.
• Liang R, Jin SD, Zhang X, Liu LJ, Rong HF. Abhd2 genes and emphysema pathogenesis research. Progr Modern Biomedicine. 2011;11:4430-3. Chinese.
• King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378(9807):1949‐61.
• Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017;389(10082):1941‐52.
• Glass DS, Grossfeld D, Renna HA, Agarwala P, Spiegler P, DeLeon J, et al. Idiopathic pulmonary fibrosis: Current and future treatment. Clin Respir J. 2022;16(2):84-96.
• Senanayake S, Harrison K, Lewis M, McNarry M, Hudson J. Patients' experiences of coping with Idiopathic Pulmonary Fibrosis and their recommendations for its clinical management. PLoS One. 2018;13(5):e0197660.
• Reinert T, Baldotto CSR, Nunes FAP, Scheliga AAS. Bleomycin-induced lung injury. J Cancer Res. 2013;2013:480608.
• Jenkins RG, Moore BB, Chambers RC, Eickelberg O, Königshoff M, Kolb M, et al. An official American Thoracic Society Workshop report: use of animal models for the preclinical assessment of potential therapies for pulmonary fibrosis. Am J Respir Cell Mol Biol. 2017;56(5):667-79.
• Moore BB, Hogaboam CM. Murine models of pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2008;294(2):L152-60.
• Stefanov AN, Fox J, Depault F, Haston CK. Positional cloning reveals strain-dependent expression of Trim16 to alter susceptibility to bleomycin-induced pulmonary fibrosis in mice. PLoS Genet. 2013;9(1):e1003203.
• Redente EF, Jacobsen KM, Solomon JJ, Lara AR, Faubel S, Keith RC, et al. Age and sex dimorphisms contribute to the severity of bleomycin-induced lung injury and fibrosis. Am J Physiol Lung Cell Mol Physiol. 2011;301(4):L510-8.
• Moeller A, Ask K, Warburton D, Gauldie J, Kolb M. The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int J Biochem Cell Biol. 2008;40(3):362-82.
• Peng R, Sridhar S, Tyagi G, Phillips JE, Garrido R, Harris P, et al. Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease. PLoS One. 2013;8(4):e59348.
• Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J. Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung. J Clin Invest. 1997;100(4):768-76.
• Bellaye PS, Yanagihara T, Granton E, Sato S, Shimbori C, Upagupta C, et al. Macitentan reduces progression of TGF-β1-induced pulmonary fibrosis and pulmonary hypertension. Eur Respir J. 2018;52(2):1701857.
• Thomas AQ, Lane K, Phillips J 3rd, Prince M, Markin C, Speer M, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med. 2002;165(9):1322-8.
• Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009;84(1):52-9.
• Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356(13):1317-26.
• Davis GS, Leslie KO, Hemenway DR. Silicosis in mice: effects of dose, time, and genetic strain. J Environ Pathol Toxicol Oncol. 1998;17(2):81-97.
• Degryse AL, Lawson WE. Progress toward improving animal models for idiopathic pulmonary fibrosis. Am J Med Sci. 2011;341(6):444-9.