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Histopathological Impact of Bleomycin on Lung Injury and Development of Mediastinal Fat-Associated Lymphoid Clusters in the Lymphoproliferative Mouse Model

Published online by Cambridge University Press:  23 May 2022

Yaser Hosny Ali Elewa*
Affiliation:
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, Japan Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Osamu Ichii
Affiliation:
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, Japan Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, Japan
Sherif Kh. A. Mohamed
Affiliation:
Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
Yasuhiro Kon
Affiliation:
Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, Japan
*
*Corresponding author: Yaser Hosny Ali Elewa, E-mail: [email protected]
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Abstract

The purpose of this study is to elucidate the impact of bleomycin on the degree of lung injury and development of mediastinal fat-associated lymphoid clusters (MFALCs) in the lymphoproliferative mouse model (MRL/MpJ-Faslpr/lpr “Lpr”) and its control strain (MRL/MpJ “MpJ”). We analyzed immune cells, the degree of proliferation, lymphatic vessels (LVs), and high endothelial venules (HEVs) in lungs and MFALCs in Lpr and MpJ mice on the 7th and 21st days following intranasal instillation of either bleomycin (BLM group) or PBS (PBS group). The BLM group showed a significant increase in the size of MFALCs, lung injury score, and positive area ratios of LVs, HEVs, and immune cells (especially macrophages, B- and T-lymphocytes) on both days 7 and 21. Interestingly, the lungs in the BLM group on day 21 showed higher collagen deposition and cellular infiltration in MpJ and Lpr, respectively. Moreover, significant positive correlations were observed between the size of MFALCs and lung injury. In conclusion, BLM could exert lung fibrosis or lymphoproliferative infiltration in chronic stages in MpJ and Lpr, respectively, and this varied effect could be due to the variations in the degree of immune cell proliferation and the development of LVs and HEVs among the studied strains.

Type
Biological Applications
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of the Microscopy Society of America

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References

Abd El-Baset, SA, Abd El-haleem, MR, Abdul-Maksoud, RS & Kattaia, AAA (2021). Mesna ameliorates acute lung injury induced by intestinal ischemia–reperfusion in rats. Sci Rep 11(1), 13356.CrossRefGoogle ScholarPubMed
Aokage, T, Seya, M, Hirayama, T, Nojima, T, Iketani, M, Ishikawa, M, Terasaki, Y, Taniguchi, A, Miyahara, N, Nakao, A, Ohsawa, I & Naito, H (2021). The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury. BMC Pulm Med 21(1), 339.CrossRefGoogle ScholarPubMed
Ashcroft, T, Simpson, JM & Timbrell, V (1988). Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 41(4), 467470.CrossRefGoogle ScholarPubMed
Bénézech, C, Luu, N-T, Walker, JA, Kruglov, AA, Loo, Y, Nakamura, K, Zhang, Y, Nayar, S, Jones, LH, Flores-Langarica, A, McIntosh, A, Marshall, J, Barone, F, Besra, G, Miles, K, Allen, JE, Gray, M, Kollias, G, Cunningham, AF, Withers, DR, Toellner, KM, Jones, ND, Veldhoen, M, Nedospasov, SA, McKenzie, ANJ & Caamaño, JH (2015). Inflammation-induced formation of fat-associated lymphoid clusters. Nat Immunol 16(8), 819828.CrossRefGoogle ScholarPubMed
Boonyarattanasoonthorn, T, Elewa, YHA, Tag-El-Din-Hassan, HT, Morimatsu, M & Agui, T (2019). Profiling of cellular immune responses to Mycoplasma pulmonis infection in C57BL/6 and DBA/2 mice. Infect Genet Evol 73, 5565.CrossRefGoogle ScholarPubMed
Cruz-Migoni, S & Caamaño, J (2016). Fat-associated lymphoid clusters in inflammation and immunity. Front Immunol 7, 612612.CrossRefGoogle ScholarPubMed
de Hilster, R, Li, M, Timens, W, Hylkema, M & Burgess, JK (2019). Chronic lung pathologies that require repair and regeneration. Stem Cell Based Ther Lung Dis 24, 112.Google Scholar
Du, L, Sánchez, C, Chen, M, Edwards, DJ & Shen, B (2000). The biosynthetic gene cluster for the antitumor drug bleomycin from Streptomyces verticillus ATCC15003 supporting functional interactions between nonribosomal peptide synthetases and a polyketide synthase. Chem Biol 7(8), 623642.CrossRefGoogle Scholar
Elewa, YHA, Elwakil, MMA, Ichii, O, Nakamura, T, Mohamed, SKA & Kon, Y (2021 a). Possible crosstalk of the immune cells within the lung and mediastinal fat-associated lymphoid clusters in the acute inflammatory lung asthma-like mouse model. Int J Mol Sci 22(13), 6878.CrossRefGoogle ScholarPubMed
Elewa, YH, Ichii, O & Kon, Y (2016). Comparative analysis of mediastinal fat-associated lymphoid cluster development and lung cellular infiltration in murine autoimmune disease models and the corresponding normal control strains. Immunology 147(1), 3040.CrossRefGoogle ScholarPubMed
Elewa, YHA, Ichii, O, Nakamura, T & Kon, Y (2021 b). Dual effect of bleomycin on histopathological features of lungs and mediastinal fat-associated lymphoid clusters in an autoimmune disease mouse model. Front Immunol 12, 665100.CrossRefGoogle Scholar
Elewa, YHA, Ichii, O, Nakamura, T & Kon, Y (2021 c). Pathological alternations of mediastinal fat-associated lymphoid cluster and lung in a streptozotocin-induced diabetic mouse model. Microsc Microanal 27(1), 187200.CrossRefGoogle Scholar
Elewa, YH, Ichii, O, Otsuka, S, Hashimoto, Y & Kon, Y (2014). Characterization of mouse mediastinal fat-associated lymphoid clusters. Cell Tissue Res 357(3), 731741.CrossRefGoogle ScholarPubMed
Elewa, YHA, Ichii, O, Takada, K, Nakamura, T, Masum, MA & Kon, Y (2018). Histopathological correlations between mediastinal fat-associated lymphoid clusters and the development of lung inflammation and fibrosis following bleomycin administration in mice. Front Immunol 9, 271.Google ScholarPubMed
Hay, J, Shahzeidi, S & Laurent, G (1991). Mechanisms of bleomycin-induced lung damage. Arch Toxicol 65(2), 8194.CrossRefGoogle ScholarPubMed
Huaux, F, Liu, T, McGarry, B, Ullenbruch, M, Xing, Z & Phan, SH (2003). Eosinophils and T lymphocytes possess distinct roles in bleomycin-induced lung injury and fibrosis. J Immunol 171(10), 54705481.CrossRefGoogle Scholar
Izbicki, G, Segel, MJ, Christensen, TG, Conner, MW & Breuer, R (2002). Time course of bleomycin-induced lung fibrosis. Int J Exp Pathol 83(3), 111119.CrossRefGoogle ScholarPubMed
Jackson-Jones, LH & Bénézech, C (2020). FALC stromal cells define a unique immunological niche for the surveillance of serous cavities. Curr Opin Immunol 64, 4249.CrossRefGoogle ScholarPubMed
Manali, ED, Moschos, C, Triantafillidou, C, Kotanidou, A, Psallidas, I, Karabela, SP, Roussos, C, Papiris, S, Armaganidis, A, Stathopoulos, GT & Maniatis, NA (2011). Static and dynamic mechanics of the murine lung after intratracheal bleomycin. BMC Pulm Med 11, 33.CrossRefGoogle ScholarPubMed
Meyer, RM, Gospodarowicz, MK, Connors, JM, Pearcey, RG, Wells, WA, Winter, JN, Horning, SJ, Dar, AR, Shustik, C, Stewart, DA, Crump, M, Djurfeldt, MS, Chen, BE & Shepherd, LE (2012). ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med 366(5), 399408.CrossRefGoogle ScholarPubMed
Peterhans, S, Landolt, P, Friedel, U, Oberhänsli, F, Dennler, M, Willi, B, Senn, M, Hinden, S, Kull, K, Kipar, A, Stephan, R & Ghielmetti, G (2020). Mycobacterium microti: Not just a coincidental pathogen for cats. Front Vet Sci 7, 1018.CrossRefGoogle ScholarPubMed
Reilly, CM & Gilkeson, GS (2002). Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice. Immunol Res 25(2), 143153.CrossRefGoogle Scholar
Ruddle, NH (2016). High endothelial venules and lymphatic vessels in tertiary lymphoid organs: Characteristics, functions, and regulation. Front Immunol 7, 491.CrossRefGoogle ScholarPubMed
Santiago-Raber, ML, Kikuchi, S, Borel, P, Uematsu, S, Akira, S, Kotzin, BL & Izui, S (2008). Evidence for genes in addition to Tlr7 in the Yaa translocation linked with acceleration of systemic lupus erythematosus. J Immunol 181(2), 15561562.CrossRefGoogle ScholarPubMed
Schafer, MJ, White, TA, Iijima, K, Haak, AJ, Ligresti, G, Atkinson, EJ, Oberg, AL, Birch, J, Salmonowicz, H, Zhu, Y, Mazula, DL, Brooks, RW, Fuhrmann-Stroissnigg, H, Pirtskhalava, T, Prakash, YS, Tchkonia, T, Robbins, PD, Aubry, MC, Passos, JF, Kirkland, JL, Tschumperlin, DJ, Kita, H & LeBrasseur, NK (2017). Cellular senescence mediates fibrotic pulmonary disease. Nat Commun 8(1), 14532.CrossRefGoogle ScholarPubMed
Smith, BM, Kirby, M, Hoffman, EA, Kronmal, RA, Aaron, SD, Allen, NB, Bertoni, A, Coxson, HO, Cooper, C, Couper, DJ, Criner, G, Dransfield, MT, Han, MK, Hansel, NN, Jacobs, DR Jr, Kaufman, JD, Lin, C-L, Manichaikul, A, Martinez, FJ, Michos, ED, Oelsner, EC, Paine, R III, Watson, KE, Benedetti, A, Tan, WC, Bourbeau, J, Woodruff, PG & Barr, RG, for the MESA Lung, C & Investigators, S (2020). Association of dysanapsis with chronic obstructive pulmonary disease among older adults. JAMA 323(22), 22682280.Google ScholarPubMed
Ware, LB & Matthay, MA (2000). The acute respiratory distress syndrome. N Engl J Med 342(18), 13341349.CrossRefGoogle ScholarPubMed
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