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Cell and Tissue Biology

, Volume 8, Issue 4, pp 344–351 | Cite as

The use of inducers of apoptosis in treatment of experimental influenza infection and prevention of chronic Postinfluenza lung lesions

  • V. V. ZarubaevEmail author
  • V. G. Tribulovich
  • S. V. Belyaevskaya
  • N. A. Barlev
Article
  • 34 Downloads

Abstract

Influenza is a respiratory infection that is widespread throughout the world. Its complications are diverse and in many cases include excessive proliferation of cells in the respiratory tract as a factor of the pathogenesis of influenza. The present work studies the effectiveness of using the apoptosis inducer 6-[3-(1-adamantide)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) for prevention of chronic lung lesions at the stage of postinfluenza pneumonia. Mice were infected with influenza virus A/mallard/Pennsylvania/10218/84(H5N2); level of virus reproduction in the lungs, specific lethality to animals, and the morphological structure of foci of postinfluenza pneumonia were then studied at the 15th day post infection. AHPN was shown to decrease the virus’ infectious activity in lung tissue by 1.2–1.5 lgEID50/0.2 mL, depending on the dose used, compared with the control group and to lead to a slight decrease of lethality of animals (the protection index being 12.5–37.5%). Use of AHPN restricted both proliferative and infiltrative components of chronic foci of postinfluenza pneumonia. It exhibited the most pronounced effect on morphology of the lung tissue when used on the fourth to seventh day after infection, i.e., in the period of the greatest activation of processes of the tissue inflammatory infiltration and regeneration of bronchiolar epithelium. Thus, use of apoptosis inducers can prevent development of postinfluenza complications with proliferative component.

Keywords

influenza postinfluenza pneumonia apoptosis apoptosis inducers AHPN chemotherapy 

Abbreviations

MLS

mean lifespan

COPD

chronic obstructive pulmonary disease

EID50

50% experimental infectious dose

LD50

50% lethal dose

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References

  1. Asaka, M., Ishikawa, I., Nakazawa, T., Tomosugi, N., Yuri, T., and Suzuki, K., Hemolytic uremic syndrome associated with influenza A virus infection in an adult renal allograft recipient: case report and review of the literature, Nephron, 2000, vol. 84, pp. 258–266.PubMedCrossRefGoogle Scholar
  2. Attarian, S. and Azulay, J.P., Infectious myopathies, Rev. Prat., 2001, vol. 51, pp. 284–288.PubMedGoogle Scholar
  3. Baky, A.A., Winkler, D.G., Hunter, N.R., Subach, J.A., Greenberg, S.D., Spjut, H.J., Estrada, R., and Kimzey, S.L., Atypia status index of respiratory cells: a measurement for the detection and monitoring of neoplastic changes in squamous cell carcinogenesis, Anal. Quant. Cytol., 1980, vol. 2, pp. 175–185.PubMedGoogle Scholar
  4. Barlev, N.A., Sayan, B.S., Candi, E., and Okorokov, A.L., The microRNA and p53 families join forces against cancer, Cell Death Differ., 2010, vol. 17, pp. 373–375.PubMedCrossRefGoogle Scholar
  5. Belum, V.R., Fontanilla, Patel, H., Lacouture, M.E., and Rodeck, U., Skin toxicity of targeted cancer agents: mechanisms and intervention, Future Oncol., 2013, vol. 9, pp. 1161–1170.PubMedCrossRefGoogle Scholar
  6. Bezuglova, T.V., Kazantseva, I.A., Lange, A., and Retig, V., Pathomorphology of chronization and outcomes of experimental mycoplasma-viral pneumonia, Arkh. Patol., 1991, vol. 53, no. 11, pp. 33–73.PubMedGoogle Scholar
  7. Conway, S.P., Simmonds, E.J., and Littlewood, J.M., Acute severe deterioration in cystic fibrosis associated with influenza A virus infection, Thorax, 1992, vol. 47, pp. 112–114.PubMedCentralPubMedCrossRefGoogle Scholar
  8. Costa, S.L., Paillaud, E., Fages, C., Rochette-Egly, C., Plassat, J.L., Jouault, H., Perzelova, A., and Tardy, M., Effects of a novel synthetic retinoid on malignant glioma in vitro: inhibition of cell proliferation, induction of apoptosis and differentiation, Eur. J. Cancer., 2001, vol. 37, pp. 520–530.PubMedCrossRefGoogle Scholar
  9. Dudek, S.E., Luig, C., Pauli, E.K., Schubert, U., and Ludwig, S., The clinically approved proteasome inhibitor PS-341 efficiently blocks influenza A virus and vesicular stomatitis virus propagation by establishing an antiviral state, J. Virol., 2010, vol. 84, pp. 9439–9451.PubMedCentralPubMedCrossRefGoogle Scholar
  10. Ekstrand, J.J., Neurologic complications of influenza, Semin. Pediatr. Neurol., 2012, vol. 19, pp. 96–100.PubMedCrossRefGoogle Scholar
  11. Ghendon, Y., Influenza-its impact and control, World Health Statistic, 1992, vol. Q 45, pp. 306–311.Google Scholar
  12. Jakab, G.J., Astry, C.L., and Warr, G., Alveolitis induced by influenza virus, Am. Rev. Respir. Dis., 1983, vol. 128, pp. 730–739.PubMedGoogle Scholar
  13. Jakab, G.J. and Hemenway, D.R., Experimental influenza virus infection, silicon dioxide polymorphs, and pulmonary fibrogenesis, J. Toxicol. Environ. Health, 1992, vol. 37, pp. 11–24.PubMedCrossRefGoogle Scholar
  14. Kadara, H., Schroeder, C.P., Lotan, D., Pisano, C., and Lotan, R., Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis, Cancer Biol. Ther., 2006, vol. 5, pp. 518–522.PubMedCrossRefGoogle Scholar
  15. Kerr, K.M., Carey, F.A., King, G., and Lamb, D., Atypical alveolar hyperplasia: relationship with pulmonary adenocarcinoma, p53 and C-erbB-2 expression, J. Pathol., 1994, vol. 174, pp. 249–256.PubMedCrossRefGoogle Scholar
  16. Kulichkova, V.A., Tsimokha, A.S., Fedorova, O.A., Moiseeva, T.N., Bottril, A., Lezina, L., Gauze, L.N., Konstantinova, I.M., Mittenberg, A.G., and Barlev, N.A., 26S Proteasome exhibits endoribonuclease activity controlled by extra-cellular stimuli, Cell Cycle, 2010, vol. 9, pp. 840–849.PubMedCrossRefGoogle Scholar
  17. Lantuejoul, S., Ferretti, G., Negoescu, A., Parent, B., and Brambilla, E., Multifocal alveolar hyperplasia associated with lymphangioleiomyomatosis in tuberous sclerosis, Histopathology, 1997, vol. 30, pp. 570–575.PubMedCrossRefGoogle Scholar
  18. Leigh, R., Ellis, R., Wattie, J., Southam, D., de, Hoogh, M., Gauldie, J., O’Byrne, P.M., and Inman, M., Dysfunction and remodeling of the mouse airway persists after resolution of acute allergen-induced airway inflammation, Am. J. Respir. Cell. Mol. Biol., 2002, vol. 27, pp. 526–535.PubMedCrossRefGoogle Scholar
  19. Lemercier, G., Burchart, M.F., and Fontanges, R., Bronchioloalveolar metaplasia during experimental influenza in mice-histological and ultrastructural study, Tohoku J. Exp. Med., 1976, vol. 118, pp. 59–79.PubMedCrossRefGoogle Scholar
  20. Loosli, C.G., Stinson, S.F., Ryan, D.P., Hardy, D.P., and Serebrin, R., The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice, Chest, 1975, vol. 67, no. 2 (suppl.), pp. 7S–14S.PubMedCrossRefGoogle Scholar
  21. Machet, L., Samimi, M., Delage, M., Paintaud, G., and Maruani, A., Systematic review of the efficacy and adverse events associated with infliximab treatment of hidradenitis suppurativa in patients with coexistent inflammatory diseases, J. Am. Acad. Dermatol., 2013, vol. 69, pp. 649–650.PubMedCrossRefGoogle Scholar
  22. Mazur, I., Wurzer, W.J., Ehrhardt, C., Pleschka, S., Puthavathana, P., Silberzahn, T., Wolff, T., Planz, O., Ludwig, and S., Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity, Cell. Microbiol., 2007, vol. 9, 1683–1694.PubMedCrossRefGoogle Scholar
  23. Mittenberg, A.G., Moiseeva, T.N., and Barlev, N.A., Role of proteasomes in transcription and their regulation by covalent modifications, Front. Biosci., 2008, vol. 13, pp. 7184–7192.PubMedCrossRefGoogle Scholar
  24. Mori, M, Morishita, H, Nakamura, H, Matsuoka, H, Yoshida, K, Kishima, Y, Zhou, Z, Kida, H, Funakoshi, T, Goya, S, Yoshida, M, Kumagai, T, Tachibana, I, Yamamoto, Y, Kawase, I, and Hayashi, S., Hepatoma-derived growth factor is involved in lung remodeling by stimulating epithelial growth, Am. J. Respir. Cell. Mol. Biol., 2004, vol. 30, pp. 459–469.PubMedCrossRefGoogle Scholar
  25. Muñoz-Fontela, C., Pazos, M., Delgado, I., Murk, W., Mungamuri, S.K., Lee, S.W., García-Sastre, A., Moran, T.M., and Aaronson, S.A., p53 Serves as a host antiviral factor that enhances innate and adaptive immune responses to influenza A virus, J. Immunol., 2011, vol. 187, pp. 6428–6436.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Nolte, K.B., Alakija, P., Oty, G., Shaw, M.W., Subbarao, K., Guarner, J., Shieh, W.J., Dawson, J.E., Morken, T., Cox, N.J., and Zaki, S.R., Influenza A virus infection complicated by fatal myocarditis, Am. J. Forensic Med. Pathol., 2000, vol. 21, pp. 375–379.PubMedCrossRefGoogle Scholar
  27. Okabe, N., Yamashita, K., Taniguchi, K., and Inouye, S., Influenza surveillance system of japan and acute encephalitis and encephalopathy in the influenza season, Pediatr. Int., 2000, vol. 42, pp. 187–191.PubMedCrossRefGoogle Scholar
  28. Pan, M., Geng, S., Xiao, S., Ren, J., Liu, Y., Li, X., Li, Z., and Peng, Z., Apoptosis induced by synthetic retinoic acid CD437 on human melanoma A375 cells involves RIG-I pathway, Arch. Dermatol. Res., 2009, vol. 301, pp. 15–20.PubMedCrossRefGoogle Scholar
  29. Planz, O., Development of cellular signaling pathway inhibitors as new antivirals against influenza, Antiviral Res., 2013, vol. 98, pp. 457–468.PubMedCrossRefGoogle Scholar
  30. Popper, H.H., Juettner-Smolle, F.M., and Pongratz, M.G., Micronodular hyperplasia of type II pneumocytes—a new lung lesion associated with tuberous sclerosis, Histopathology, 1991, vol. 18, pp. 347–354.PubMedCrossRefGoogle Scholar
  31. Postow, M.A., Harding, J., and Wolchok, J.D., Targeting immune checkpoints: releasing the restraints on anti-tumor immunity for patients with melanoma, Cancer, 2012, vol. 18, pp. 153–159.Google Scholar
  32. Qiao, J., Zhang, M., Bi, J., Wang, X., Deng, G., He, G., Luan, Z., Lv, N., Xu, T., and Zhao, L., Pulmonary fibrosis induced by H5N1 viral infection in mice, Respir. Res., 2009, vol. 10, pp. 107.PubMedCentralPubMedCrossRefGoogle Scholar
  33. Reed, L.J. and Muench, H., A simple method of estimating fifty percent endpoints, Am. J. Hyg., 1938, vol. 27, pp. 493–497.Google Scholar
  34. Rott, O., Herzog, S., and Cash, E., Autoimmunity caused by host cell protein-containing viruses, Med. Microbiol. Immunol. (Berlin), 1994, vol. 183, pp. 195–204.CrossRefGoogle Scholar
  35. Schlesinger, C., Veeraraghavan, S., and Koss, M.N., Constructive (obliterative) eronchiolitis, Curr. Opin. Pulm. Med., 1998, vol. 4, pp. 288–293.PubMedCrossRefGoogle Scholar
  36. Shen, Y., Wang, X., Guo, L., Qiu, Y., Li, X., Yu, H., Xiang, H., Tong, G., and Ma, Z., Influenza A virus induces p53 accumulation in a biphasic pattern, Biochem. Biophys. Res. Commun., 2009, vol. 382, pp. 331–335.PubMedCrossRefGoogle Scholar
  37. Tribulovich, V.G., Development of methods of formation of C-C bond in the synthesis of adamantly-substituted retinoids, Extended Abstract of Candidate’s (Biol.) Dissertation, St. Petersburg, 2010.Google Scholar
  38. Turpin, E., Luke, K., Jones, J., Tumpey, T., Konan, K., and Schultz-Cherry, S., Influenza virus infection increases p53 activity: role of p53 in cell death and viral replication, J. Virol., 2005, vol. 79, pp. 8802–8811.PubMedCentralPubMedCrossRefGoogle Scholar
  39. Veenstra, R.P., Boelen, C.C., Zijlstra, J.G., Bos, A.P., and Ligtenberg, J.J., Influenza A pneumonia, Ned. Tijdschr.. Geneeskd., 2000, vol. 144, pp. 1937–1941.PubMedGoogle Scholar
  40. Vilchez, R.A., Fung, J.J., and Kusne, S., Influenza A myocarditis developing in an adult liver transplant recipient despite vaccination: a case report and review of the literature, Transplantation, 2000, vol. 70, pp. 543–545.PubMedCrossRefGoogle Scholar
  41. Wang, X., Deng, X., Yan, W., Zhu, Z., Shen, Y., Qiu, Y., Shi, Z., Shao, D., Wei, J., Xia, X., and Ma, Z., Stabilization of p53 in influenza A virus-infected cells is associated with compromised MDM2-mediated ubiquitination of p53, J. Biol. Chem., 2012, vol. 287, pp. 18366–18375.PubMedCentralPubMedCrossRefGoogle Scholar
  42. Zambon, M., Epidemiology and pathogenesis of influenza, J. Antimicrob. Chemother., 1999, vol. 44, pp. B3–9.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • V. V. Zarubaev
    • 1
    Email author
  • V. G. Tribulovich
    • 1
  • S. V. Belyaevskaya
    • 1
  • N. A. Barlev
    • 2
  1. 1.Influenza Research InstituteMinistry of HealthSt. PetersburgRussia
  2. 2.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

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