Abstract
Reactive oxygen species (ROS) produced by phagocytic cells of the innate immune system play an important role in the first line of defense of an organism against pathogens. The main source of ROS in all types of phagocytes is the membrane-associated multimolecular NADPH oxidase complex. The formation of this complex and its activity depend on many factors, which can both intensify and suppress the ROS generation. However, in recent years substantial evidence has accumulated indicating the existence of poorly studied mechanisms for the restriction of ROS production by phagocytes, which are involved in the protection of host tissues against the damaging action of oxygen radicals in inflammation loci. Our previous data and the results of other authors indicate that one link of this restriction system may be related to the immunomodulating activity of the extracellular pool of 70 kDa heat shock protein (HSP70). In the present study, in vitro cultures of phagocytes and NADPH oxidase inhibitors were used to analyze a possible relationship between the suppressing effect of exogenous HSP70 on ROS production by phagocytes and the interaction of HSP70 with the subunits of this enzyme complex. The results confirmed the literature data on the ability of exogenous HSP70 to modulate the NADPH oxidase activity and demonstrated for the first time the inhibitory effect of this protein on the intensity of intracellular ROS generation in phagocytes.
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Abbreviations
- Apo:
-
apocyanin
- DCF-DA:
-
2′,7′-dichlorofluorescein diacetate
- BM:
-
bone marrow
- BSA:
-
bovine serum albumin
- DPI:
-
diphenyliodonium
- fMLP:
-
N-formyl-methionylleucyl-phenylananine
- HSP70:
-
the 70 kDa heat shock protein
- LPS:
-
lipopolysaccharide
- NOX:
-
NADPH oxidase
- ROS:
-
reactive oxygen species
References
Touyz, R.M., Briones, A.M., Sedeek, M., Burger, D., and Montezano, A.C., Mol. Interv., 2011, vol. 11, pp. 27–35.
Droge, W., Physiol. Rev., 2002, vol. 82, pp. 47–95.
Ponomarev, A.D., Semenkov, V.F., and Sapozhnikov, A.M., Immunologiya, 2005, vol. 26, pp. 72–75.
Yurinskaya, M.M., Vinokurov, M.G., Zatsepina, O.G., Garbuz, D.G., Guzhova, I.V., Rozhkova, E.A., Suslikov, A.V., Karpov, V.L., and Evgen’ev, M.B., Dokl. Biol. Sci., 2009, vol. 426, pp. 298–301.
Parsell, D.A. and Lindquist, S., Annu. Rev. Genet., 1993, vol. 27, pp. 437–496.
Johnson, J.D. and Fleshner, M., J. Leukoc. Biol., 2006, vol. 79, pp. 425–434.
Walsh, R.C., Koukoulas, I., Garnham, A., Moseley, P.L., Hargreaves, M., and Febbraio, M.A., Cell Stress Chaperones, 2001, vol. 6, pp. 386–393.
Pockley, A.G., De Faire, U., Kiessling, R., Lemne, C., Thulin, T., and Frostegard, J., J. Hypertens., 2002, vol. 20, pp. 1815–1820.
Srivastava, P., Annu Rev. Immunol., 2002, vol. 20, pp. 395–425.
Multhoff, G., Int. J. Hyperthermia, 2002, vol. 18, pp. 576–585.
Asea, A., Kraeft, S.K., Kurt-Jones, E.A., Stevenson, M.A., Chen, L.B., Finberg, R.W., Koo, G.C., and Calderwood, S.K., Nat. Med., 2000, vol. 6, pp. 435–442.
Chen, F., Yu, Y., Qian, J., Wang, Y., Cheng, B., Dimitropoulou, C., Patel, V., Chadli, A., Rudic, R.D., Stepp, D.W., Catravas, J.D., and Fulton, D.J., Arterioscler. Thromb. Vasc. Biol., 2012, vol. 32, pp. 2989–2999.
Je, J.H., Kim, D.Y., Roh, H.J., Pak, C., Kim, D.H., Byamba, D., Jee, H., Kim, T.G., Park, J.M., Lee, S.K., and Lee, M.G., Scand. J. Immunol., 2013, vol. 78, no. 3, pp. 238–247.
Maridonneau-Parini, I., Clerc, J., and Polla, B.S., Biochem. Biophys. Res. Communs., 1988, vol. 154, pp. 179–186.
Lundqvist, H. and Dahlgren, C., Free Radic. Biol. Med., 1996, vol. 20, pp. 785–792.
Lundqvist, H., Follin, P., Khalfan, L., and Dahlgren, C., J. Leukocyte Biol., 1996, vol. 59, pp. 270–279.
Panaro, M.A. and Mitolo, V., Immunopharmacol. Immunotoxicol., 1999, vol. 21, pp. 397–419.
Touyz, R.M., Hypertension, 2008, vol. 51, pp. 172–174.
O’Donnell, B.V., Tew, D.G., Jones, O.T., and England, P.J., Biochem. J., 1993, vol. 290, pt. 1, pp. 41–49.
Herodin, F. and Benichou, G., J. Leukocyte Biol., 1987, vol. 42, pp. 76–83.
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Original Russian Text © N.I. Troyanova, M.A. Shevchenko, A.A. Boyko, P.P. Mirzoev, M.A. Pertseva, E.I. Kovalenko, A.M. Sapozhnikov, 2015, published in Bioorganicheskaya Khimiya, 2015, Vol. 41, No. 3, pp. 305–315.
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Troyanova, N.I., Shevchenko, M.A., Boyko, A.A. et al. Modulating effect of extracellular HSP70 on generation of reactive oxigen species in populations of phagocytes. Russ J Bioorg Chem 41, 271–279 (2015). https://doi.org/10.1134/S1068162015030097
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DOI: https://doi.org/10.1134/S1068162015030097