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Molecular Mechanisms of Regulation of Functional Activity of Mononuclear Phagocytes by Leptin

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Abstract

Leptin is a peptide hormone synthesized by adipocytes. The main function of leptin is associated with regulation of the body energetic balance and restriction of excess accumulation of fat. This review considers in detail the involvement of leptin in regulation of fundamental effector functions of mononuclear phagocytes, which express receptors for this hormone. Possible molecular mechanisms of modulation by leptin of phagocytic activity, oxygen-dependent microbicidity, and nitric oxide generation by mononuclear phagocytes are analyzed, as well as the role of leptin in the formation of the produced cytokine pattern. The data presented suggest that the regulation of mononuclear phagocytes by leptin is associated with activation of the JAK/STAT signaling pathway, which leads to stimulation of phagocytosis, production of oxygen and nitrogen reactive species, and also to increase in secretion of pro-inflammatory cytokines.

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Abbreviations

EPR:

endoplasmic reticulum

AP 1:

activating protein-1

CD:

membrane molecules of lymphomyeloid cells

CaN:

calcineurine

CR:

receptor to complement components

DAG:

diacylglycerol

ERK:

extracellularly regulated protein kinase

FcR:

Fc-receptors

G-CSF:

granulocytic colony-stimulating factor

GM-CSF:

granulocytic-macrophagal colony-stimulating factor

IL:

interleukins

IP3 :

inositol 1,4,5-triphosphate

JNK:

c-Jun-NH2-terminal protein kinase

MAPK:

mitogen-activated protein kinase

MARCKS:

myristoylated alanine-rich C kinase substrate, or actinogelin

MLCK:

myosin light-chain kinase, or ERKII-induced MLC kinase

MR:

mannose receptor

NFAT:

nuclear factor of activated T-cells

NF-kB:

nuclear factor kB

Ob-R:

leptin receptor

PKC:

protein kinase C

PLC:

phospholipase C

PLA2 :

phospholipase A2

PIP2 :

phosphatidylinositol 4,5-diphosphate

PtdIns(3,4,5)P3 :

phosphatidylinositide 3,4,5-triphosphate

PI3-K:

phosphatidylinositol-3 kinase

STAT:

proteins of signal transduction and activation of transcription

Sam68:

RNA-binding protein

SOCS-3:

suppressor of cytokine signal transduction

Th:

T-helpers

TNF-α:

tumor necrosis factor α

REFERENCES

  1. Flier, J. S., and Maratos-Flier, E. (1998) Cell, 92, 437–440.

    Article  PubMed  Google Scholar 

  2. Santos-Alvarez, J., Goberna, R., and Sanchez-Margalet, V. (1999) Cell Immunol., 194, 6–11.

    Article  PubMed  Google Scholar 

  3. Caldefie-Chezet, F., Poulin, A., and Vasson, M. P. (2003) Radical Res., 8, 809–814.

    Article  Google Scholar 

  4. Bates, S. H., and Myers, M. G. (2004) J. Mol. Med., 82, 12–20.

    Article  PubMed  Google Scholar 

  5. Fantuzzi, G., and Faggioni, R. (2000) J. Leukocyte Biol., 68, 437–446.

    PubMed  Google Scholar 

  6. Zhao, Y., Sun, R., You, L., Gao, C., and Tian, Z. (2003) Biochem. Biophys. Res. Commun., 300, 247–252.

    Article  PubMed  Google Scholar 

  7. Sweeney, G. (2002) Cell Signaling, 14, 655–663.

    Article  Google Scholar 

  8. Bennett, B. D., Solar, G. P., Yuan, J. Q., Mathias, J., Thomas, G. R., and Matthews, W. (1996) Current Biol., 6, 1170–1180.

    Google Scholar 

  9. Bouloumie, A., Marumo, T., Lafontan, M., and Busse, R. (1999) FASEB J., 13, 1231–1238.

    PubMed  Google Scholar 

  10. Fujita, Y., Murakami, M., Ogawa, Y., Masuzaki, H., Tanaka, M., Ozaki, S., Nakao, K., and Mimori, T. (2002) Clin. Exp. Immunol., 128, 21–26.

    Article  PubMed  Google Scholar 

  11. Gainsford, T., Willson, T. A., Metcalf, D., Handman, E., McFarlane, C., Ashley, N. G., Nicola, N. A., Alexander, W. S., and Hilton, D. J. (1996) Proc. Natl. Acad. Sci. USA, 93, 14564–14568.

    Article  PubMed  Google Scholar 

  12. Ahima, R. S., and Flier, J. S. (2000) Ann. Rev. Physiol., 62, 413–437.

    Article  Google Scholar 

  13. Loffreda, S., Yang, S. Q., Lin, H. Z., Karp, C. L., Brengman, M. L., Wang, D. J., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., Lane, M. D., and Diehl, A. M. (1998) FASEB J., 12, 57–65.

    PubMed  Google Scholar 

  14. Najib, S., and Sanchez-Margalet, V. (2002) Cell. Immunol., 220, 143–149.

    Article  PubMed  Google Scholar 

  15. Gainsford, T., and Alexander, W. S. (1999) Mol. Biotechnol., 11, 149–158.

    PubMed  Google Scholar 

  16. Fong, T. M., Huang, R. R., Tota, M. R., Mao, C., Smith, T., Varnerin, J., Karpiyskiy, V. V., Krause, J. E., and van der Ploeg, L. H. (1998) Mol. Pharmacol., 53, 234–240.

    PubMed  Google Scholar 

  17. Bjorbaek, C., Uotani, S., da Silva, B., and Flier, J. (1997) J. Biol. Chem., 272, 32686–32695.

    PubMed  Google Scholar 

  18. Tartaglia, L. A. (1997) J. Biol. Chem., 272, 6093–6096.

    PubMed  Google Scholar 

  19. Baumann, H., Morella, K. K., White, D. W., Dembski, M., Bailon, P. S., Kim. H., Lai, C. F., and Tartaglia, L. A. (1996) Proc. Natl. Acad. Sci. USA, 93, 8374–8378.

    Article  PubMed  Google Scholar 

  20. Martin-Romero, C., and Sanchez-Margalet, V. (2001) Cell. Immunol., 212, 83–91.

    Article  PubMed  Google Scholar 

  21. Sanchez-Margalet, C., Martin-Romero, J., Santos-Alvarez, R., Goberna, S., Najib, C., and Gonzalez-Yanes, C. (2003) Clin. Exp. Immunol., 133, 11–19.

    Article  PubMed  Google Scholar 

  22. Martin-Romero, C., Santos-Alvarez, J., Goberna, R., and Sanchez-Margalet, V. (2000) Cell. Immunol., 199, 15–24.

    Article  PubMed  Google Scholar 

  23. Attoub, S., Noe, V., Pirola, L., Bruyneel, E., Chastre, E., Mareel, M., Wymann, M. P., and Gespach, C. (2000) FASEB J., 14, 2329–2338.

    Article  PubMed  Google Scholar 

  24. Rouet-Benzineb, P., Aparicio, T., Guilmeau, S., Pouzet, C., Descatoire, V., Buyse, M., and Bado, A. (2004) J. Biol. Chem., 279, 16495–16502.

    Article  PubMed  Google Scholar 

  25. Zarkesh-Esfahani, H., Pockley, A. G., Metcalfe, R. A., Bidlingmaier, M., Wu, Z., Ajami, A., Weetman, A. P., Strasburger, C. J., and Ross, R. J. (2001) J. Immunol., 167, 4593–4599.

    PubMed  Google Scholar 

  26. Aderem, A., and Underhill, D. M. (1999) Ann. Rev., 17, 593–623.

    Google Scholar 

  27. Greenberg, S. (2001) J. Cell Sci., 114, 1039–1040.

    PubMed  Google Scholar 

  28. Raeder, E. M., Mansfield, P. J., Hinkovska-Galcheva, V., Kjeldsen, L., Shayman, J. A., and Boxer, L. A. (1999) Blood, 93, 686–693.

    PubMed  Google Scholar 

  29. Mackay, D. J., and Hall, A. (1998) J. Biol. Chem., 273, 20685–20688.

    Article  PubMed  Google Scholar 

  30. Kuklina, E. M., and Shirshev, S. V. (2001) Biochemistry (Moscow), 66, 467–475.

    Article  Google Scholar 

  31. Dreyer, M. G., Juge-Aubry, C. E., Gabay, C., Lang, U., Rohner-Jeanrenaud, F., Dayer, J. M., and Meier, C. A. (2003) Biochem. J., 370, 591–599.

    Article  PubMed  Google Scholar 

  32. Dixit, V. D., Mielenz, M., Taub, D. D., and Parvizi, N. (2003) Endocrinology, 144, 5595–5603.

    Article  PubMed  Google Scholar 

  33. Mancuso, P., Gottschalk, A., Phare, S. M., Peters-Golden, M., Lukacs, N. W., and Huffnagle, G. (2002) J. Immunol., 168, 4018–4024.

    PubMed  Google Scholar 

  34. Denhardt, D. T. (1996) Biochem. J., 318, 729–747.

    PubMed  Google Scholar 

  35. Crowley, M. T., Costello, P. S., Fitzer-Attas, C. J., Turner, M., Meng, F., Lowell, C., Tybulewicz, V. L., and DeFranco, A. L. (1997) J. Exp. Med., 186, 1027–1039.

    Article  PubMed  Google Scholar 

  36. Cox, D., Tseng, C. C., Bjekic, G., and Greenberg, S. (1999) J. Biol. Chem., 274, 1240–1247.

    Article  PubMed  Google Scholar 

  37. Dekker, L. V., Leitges, M., Altschuler, G., Mistry, N., McDermott, A., Roes, J., and Segal, A. W. (2000) J. Biochem., 347, 285–289.

    Article  Google Scholar 

  38. Shirshev, S. V. (2002) Mechanisms of Immunoendocrine Control of Reproduction [in Russian], Vol. 2, Ural Division of Russian Academy of Sciences Publishers, Yekaterinburg.

    Google Scholar 

  39. Sanchez-Pozo, C., Rodriguez-Bano, J., Dominguez-Castellano, A., Muniain, M. A., Goberna, R., and Sanchez-Margalet, V. (2003) Clin. Exp. Immunol., 134, 464–469.

    Article  PubMed  Google Scholar 

  40. Mancuso, P., Canetti, C., Gottschalk, A., Tithof, P. K., and Peters-Golden, M. (2004) Am. J. Physiol. Lung Cell Mol. Physiol., 287, L126–L135.

    Google Scholar 

  41. Nielson, C. P., Bayer, C., Hodson, S., and Hadjokas, N. (1992) J. Immunol., 149, 4036–4040.

    PubMed  Google Scholar 

  42. Raso, G. M., Pacilio, M., Esposito, E., Coppola, A., Carlo, R., and Meli, R. (2002) Br. J. Pharmacol., 137, 799–804.

    Article  PubMed  Google Scholar 

  43. Konturek, P. C., Brzozowski, T., Sulekova, Z., Brzozowska, I., Duda, A., Meixner, H., Hahn, E. G., and Konturek, S. J. (2001) Eur. J. Pharmacol., 414, 87–97.

    Article  PubMed  Google Scholar 

  44. Otero, M., Gomez Reino, J. J., and Gualillo, O. (2003) Arthritis Rheum., 48, 404–409.

    Article  PubMed  Google Scholar 

  45. Fruhbeck, G. (1999) Diabetes, 48, 903–908.

    PubMed  Google Scholar 

  46. Refici, M. L., Metzger, D. W., Arulanandam, B. P., Lennartz, M. R., and Loegering, D. J. (2001) Am. J. Physiol. Regul. Integr. Comp. Physiol., 280, R1037–R1044.

    PubMed  Google Scholar 

  47. Yamamoto, Y., Klein, T. W., and Friedman, H. (1997) Infect. Immun., 65, 1077–1082.

    PubMed  Google Scholar 

  48. Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., and Henson, P. M. (1998) J. Clin. Invest., 101, 890–898.

    PubMed  Google Scholar 

  49. Sarraf, P., Frederich, R. C., Turner, E. M., Ma, G., Jaskowiak, N. T., Rivet, D. J., Flier, J. S., Lowell, B. B., Fraker, D. L., and Alexander, H. R. (1997) J. Exp. Med., 185, 171–175.

    Article  PubMed  Google Scholar 

  50. Maingrette, F., and Renier, G. (2003) Diabetes, 52, 2121–2128.

    PubMed  Google Scholar 

  51. Faggioni, R., Fantuzzi, G., Fuller, J., Dinarello, C. A., Feingold, K. R., and Grunfeld, C. (1998) Am. J. Physiol., 274, 204–208.

    Google Scholar 

  52. Vallejo, J. G., Knuefermann, P., Mann, D. L., and Sivasubramanian, N. (2000) J. Immunol., 165, 419–425.

    PubMed  Google Scholar 

  53. Alonzi, T., Maritano, D., Gorgoni, B., Rizzuto, G., Libert, C., and Poli, V. (2001) Mol. Cell Biol., 21, 1621–1632.

    Article  PubMed  Google Scholar 

  54. Wang, L., Walia, B., Evans, J., Gewirtz, A. T., Merlin, D., and Sitaraman, S. V. (2003) J. Immunol., 171, 3194–3201.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Ecology and Genetics of Microorganisms, Ural Branch, Russian Academy of Sciences, ul. Goleva 13, 614081, Perm, Russia

    S. V. Shirshev & E. G. Orlova

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  1. S. V. Shirshev
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Translated from Biokhimiya, Vol. 70, No. 8, 2005, pp. 1021–1029.

Original Russian Text Copyright © 2005 by Shirshev, Orlova.

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Shirshev, S.V., Orlova, E.G. Molecular Mechanisms of Regulation of Functional Activity of Mononuclear Phagocytes by Leptin. Biochemistry (Moscow) 70, 841–847 (2005). https://doi.org/10.1007/s10541-005-0193-1

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