Skip to main content
Top
Published in: Immunologic Research 5/2018

Open Access 01-10-2018 | Original Article

Leptin receptor is expressed by tissue mast cells

Authors: Paulina Żelechowska, Magdalena Wiktorska, Sylwia Różalska, Olga Stasikowska-Kanicka, Małgorzata Wągrowska-Danilewicz, Justyna Agier, Ewa Brzezińska-Błaszczyk

Published in: Immunologic Research | Issue 5/2018

Login to get access

Abstract

Leptin, the adipose tissue-derived product of the obese (ob) gene, is known to function as the hormone of energy expenditure. It has also been established that leptin regulates immune and inflammatory processes. All leptin-induced biological activities depend on binding to the membrane-spanning leptin receptor (Ob-R), belonging to the class I cytokine receptor family. The available data relating to the Ob-R on mature mast cells (MCs), and consequently leptin significance in the modulation of MC activity within the tissue, are limited. Immunohistochemistry was used to establish Ob-R expression by MCs in the mesenteric adipose tissue. Flow cytometry and confocal microscopy were used to evaluate both constitutive and leptin-induced expression of Ob-R on freshly isolated peritoneal MCs. MCs in the mesenteric adipose tissue and native peritoneal MCs express Ob-R constitutively. Additionally, leptin influences its receptor expression on these cells. Leptin at lower concentrations caused Ob-R expression increase both at the cell surface and in the cell interior. MC stimulation with higher concentrations of leptin results in a decline of Ob-R from the cell surface and significant enhancement of this receptor not only in the nuclear region but also in the endoplasmic reticulum. In conclusion, one can be assumed that leptin regulates MC activity within tissues. These findings might provide an additional link among the leptin, innate immune function, and inflammatory processes and diseases.
Literature
1.
go back to reference Barrenetxe J, Villaro AC, Guembe L, Pascual I, Muñoz-Navas M, Barber A, et al. Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes. Gut. 2002;50:797–802.CrossRef Barrenetxe J, Villaro AC, Guembe L, Pascual I, Muñoz-Navas M, Barber A, et al. Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes. Gut. 2002;50:797–802.CrossRef
2.
go back to reference Booth A, Magnuson A, Fouts J, Foster MT. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Invest. 2016;26:25–42. Booth A, Magnuson A, Fouts J, Foster MT. Adipose tissue: an endocrine organ playing a role in metabolic regulation. Horm Mol Biol Clin Invest. 2016;26:25–42.
3.
go back to reference Bozan G, Dogruel N. Serum leptin and bone metabolism parameters in obese children. Biomed Res. 2017;28:3607–12. Bozan G, Dogruel N. Serum leptin and bone metabolism parameters in obese children. Biomed Res. 2017;28:3607–12.
4.
go back to reference Bruno A, Conus S, Schmid I, Simon HU. Apoptotic pathways are inhibited by leptin receptor activation in neutrophils. J Immunol. 2005;174:8090–6.CrossRef Bruno A, Conus S, Schmid I, Simon HU. Apoptotic pathways are inhibited by leptin receptor activation in neutrophils. J Immunol. 2005;174:8090–6.CrossRef
5.
go back to reference Buyse M, Ovesjö ML, Goïot H, Guilmeau S, Péranzi G, Moizo L, et al. Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve. Eur J Neurosci. 2001;14:64–72.CrossRef Buyse M, Ovesjö ML, Goïot H, Guilmeau S, Péranzi G, Moizo L, et al. Expression and regulation of leptin receptor proteins in afferent and efferent neurons of the vagus nerve. Eur J Neurosci. 2001;14:64–72.CrossRef
6.
go back to reference Caraffa A, Conti C, D Ovidio C, Gallenga CE, Tettamanti L, Mastrangelo F, et al. New concepts in neuroinflammation: mast cells pro-inflammatory and anti-inflammatory cytokine mediators. J Biol Regul Homeost Agents. 2018;32:449–54.PubMed Caraffa A, Conti C, D Ovidio C, Gallenga CE, Tettamanti L, Mastrangelo F, et al. New concepts in neuroinflammation: mast cells pro-inflammatory and anti-inflammatory cytokine mediators. J Biol Regul Homeost Agents. 2018;32:449–54.PubMed
7.
go back to reference Conus S, Bruno A, Simon HU. Leptin is an eosinophil survival factor. J Allergy Clin Immunol. 2005;116:1228–34.CrossRef Conus S, Bruno A, Simon HU. Leptin is an eosinophil survival factor. J Allergy Clin Immunol. 2005;116:1228–34.CrossRef
8.
go back to reference Dayakar A, Chandrasekaran S, Veronica J, Maurya R. Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs. Exp Parasitol. 2016;160:54–9.CrossRef Dayakar A, Chandrasekaran S, Veronica J, Maurya R. Leptin induces the phagocytosis and protective immune response in Leishmania donovani infected THP-1 cell line and human PBMCs. Exp Parasitol. 2016;160:54–9.CrossRef
9.
go back to reference De Matteis G, Grandoni F, Scatà MC, Catizone A, Reale A, Crisà A, et al. Evaluation of leptin receptor expression on buffalo leukocytes. Vet Immunol Immunopathol. 2016;177:16–23.CrossRef De Matteis G, Grandoni F, Scatà MC, Catizone A, Reale A, Crisà A, et al. Evaluation of leptin receptor expression on buffalo leukocytes. Vet Immunol Immunopathol. 2016;177:16–23.CrossRef
10.
go back to reference De Rosa V, Procaccini C, Calì G, Pirozzi G, Fontana S, Zappacosta S, et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity. 2007;26:241–55.CrossRef De Rosa V, Procaccini C, Calì G, Pirozzi G, Fontana S, Zappacosta S, et al. A key role of leptin in the control of regulatory T cell proliferation. Immunity. 2007;26:241–55.CrossRef
11.
go back to reference DeBruin EJ, Gold M, Lo BC, Snyder K, Cait A, Lasic N, et al. Mast cells in human health and disease. Methods Mol Biol. 2015;1220:93–119.CrossRef DeBruin EJ, Gold M, Lo BC, Snyder K, Cait A, Lasic N, et al. Mast cells in human health and disease. Methods Mol Biol. 2015;1220:93–119.CrossRef
12.
go back to reference Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, et al. Role of leptin in the activation of immune cells. Mediat Inflamm. 2010;2010:568343.CrossRef Fernández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, et al. Role of leptin in the activation of immune cells. Mediat Inflamm. 2010;2010:568343.CrossRef
13.
go back to reference Gan L, Guo K, Cremona ML, McGraw TE, Leibel RL, Zhang Y. TNF-α up-regulates protein level and cell surface expression of the leptin receptor by stimulating its export via a PKC-dependent mechanism. Endocrinology. 2012;153:5821–33.CrossRef Gan L, Guo K, Cremona ML, McGraw TE, Leibel RL, Zhang Y. TNF-α up-regulates protein level and cell surface expression of the leptin receptor by stimulating its export via a PKC-dependent mechanism. Endocrinology. 2012;153:5821–33.CrossRef
14.
go back to reference Gilmartin L, Tarleton CA, Schuyler M, Wilson BS, Oliver JM. A comparison of inflammatory mediators released by basophils of asthmatic and control subjects in response to high-affinity IgE receptor aggregation. Int Arch Allergy Immunol. 2008;145:182–92.CrossRef Gilmartin L, Tarleton CA, Schuyler M, Wilson BS, Oliver JM. A comparison of inflammatory mediators released by basophils of asthmatic and control subjects in response to high-affinity IgE receptor aggregation. Int Arch Allergy Immunol. 2008;145:182–92.CrossRef
15.
go back to reference Hsuchou H, He Y, Kastin AJ, Tu H, Markadakis EN, Rogers RC, et al. Obesity induces functional astrocytic leptin receptors in hypothalamus. Brain. 2009;132:889–902.CrossRef Hsuchou H, He Y, Kastin AJ, Tu H, Markadakis EN, Rogers RC, et al. Obesity induces functional astrocytic leptin receptors in hypothalamus. Brain. 2009;132:889–902.CrossRef
16.
go back to reference Karpov V, Ilarraza R, Catalli A, Kulka M. Cysteinyl leukotrienes C4 and D4 downregulate human mast cell expression of toll-like receptors 1 through 7. J Biol Regul Homeost Agents. 2018;32:233–9.PubMed Karpov V, Ilarraza R, Catalli A, Kulka M. Cysteinyl leukotrienes C4 and D4 downregulate human mast cell expression of toll-like receptors 1 through 7. J Biol Regul Homeost Agents. 2018;32:233–9.PubMed
17.
go back to reference Kwon O, Kim KW, Kim MS. Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci. 2016;73:1457–77.CrossRef Kwon O, Kim KW, Kim MS. Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci. 2016;73:1457–77.CrossRef
18.
go back to reference Mastrangelo F, Frydas I, Ronconi G, Kritas SK, Tettamanti L, Caraffa A, et al. Low-grade chronic inflammation mediated by mast cells in fibromyalgia: role of IL-37. J Biol Regul Homeost Agents. 2018;32:195–8.PubMed Mastrangelo F, Frydas I, Ronconi G, Kritas SK, Tettamanti L, Caraffa A, et al. Low-grade chronic inflammation mediated by mast cells in fibromyalgia: role of IL-37. J Biol Regul Homeost Agents. 2018;32:195–8.PubMed
19.
go back to reference Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol. 2005;174:6820–8.CrossRef Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol. 2005;174:6820–8.CrossRef
20.
go back to reference Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol Rev. 2018;282:121–50.CrossRef Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol Rev. 2018;282:121–50.CrossRef
21.
go back to reference Pandit R, Beerens S, Adan RAH. Role of leptin in energy expenditure: the hypothalamic perspective. Am J Physiol Regul Integr Comp Phys. 2017;312:R938–47.CrossRef Pandit R, Beerens S, Adan RAH. Role of leptin in energy expenditure: the hypothalamic perspective. Am J Physiol Regul Integr Comp Phys. 2017;312:R938–47.CrossRef
22.
go back to reference Pastwińska J, Agier J, Dastych J, Brzezińska-Błaszczyk E. Mast cells as the strength of the inflammatory process. Pol J Pathol. 2017;68:187–96.CrossRef Pastwińska J, Agier J, Dastych J, Brzezińska-Błaszczyk E. Mast cells as the strength of the inflammatory process. Pol J Pathol. 2017;68:187–96.CrossRef
23.
go back to reference Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J. Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol. 2012;56:597–607.CrossRef Paz-Filho G, Mastronardi C, Franco CB, Wang KB, Wong ML, Licinio J. Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications. Arq Bras Endocrinol Metabol. 2012;56:597–607.CrossRef
24.
go back to reference Pérez-Pérez A, Vilariño-García T, Fernández-Riejos P, Martín-González J, Segura-Egea JJ, Sánchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017;35:71–84.CrossRef Pérez-Pérez A, Vilariño-García T, Fernández-Riejos P, Martín-González J, Segura-Egea JJ, Sánchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine Growth Factor Rev. 2017;35:71–84.CrossRef
25.
go back to reference Ramos-Lobo AM, Donato J Jr. The role of leptin in health and disease. Temperature. 2017;4:258–91.CrossRef Ramos-Lobo AM, Donato J Jr. The role of leptin in health and disease. Temperature. 2017;4:258–91.CrossRef
26.
go back to reference Stylianou C, Galli-Tsinopoulou A, Farmakiotis D, Rousso I, Karamouzis M, Koliakos G, et al. Ghrelin and leptin levels in obese adolescents. Relationship with body fat and insulin resistance. Hormones. 2007;6:295–303.CrossRef Stylianou C, Galli-Tsinopoulou A, Farmakiotis D, Rousso I, Karamouzis M, Koliakos G, et al. Ghrelin and leptin levels in obese adolescents. Relationship with body fat and insulin resistance. Hormones. 2007;6:295–303.CrossRef
27.
go back to reference Suzukawa M, Koketsu R, Baba S, Igarashi S, Nagase H, Yamaguchi M, et al. Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells. Am J Physiol Lung Cell Mol Phys. 2015;309:L801–11. Suzukawa M, Koketsu R, Baba S, Igarashi S, Nagase H, Yamaguchi M, et al. Leptin enhances ICAM-1 expression, induces migration and cytokine synthesis, and prolongs survival of human airway epithelial cells. Am J Physiol Lung Cell Mol Phys. 2015;309:L801–11.
28.
go back to reference Suzukawa M, Nagase H, Ogahara I, Han K, Tashimo H, Shibui A, et al. Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils. J Immunol. 2011;186:5254–60.CrossRef Suzukawa M, Nagase H, Ogahara I, Han K, Tashimo H, Shibui A, et al. Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils. J Immunol. 2011;186:5254–60.CrossRef
29.
go back to reference Taildeman J, Pérez-Novo CA, Rottiers I, Ferdinande L, Waeytens A, De Colvenaer V, et al. Human mast cells express leptin and leptin receptors. Histochem Cell Biol. 2009;131:703–11.CrossRef Taildeman J, Pérez-Novo CA, Rottiers I, Ferdinande L, Waeytens A, De Colvenaer V, et al. Human mast cells express leptin and leptin receptors. Histochem Cell Biol. 2009;131:703–11.CrossRef
30.
go back to reference Tang CH, Lu DY, Yang RS, Tsai HY, Kao MC, Fu WM, et al. Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol. 2007;179:1292–302.CrossRef Tang CH, Lu DY, Yang RS, Tsai HY, Kao MC, Fu WM, et al. Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol. 2007;179:1292–302.CrossRef
31.
go back to reference Żelechowska P, Agier J, Kozłowska E, Brzezińska-Błaszczyk E. Mast cells participate in chronic low-grade inflammation within adipose tissue. Obes Rev. 2018;19:686–97.CrossRef Żelechowska P, Agier J, Kozłowska E, Brzezińska-Błaszczyk E. Mast cells participate in chronic low-grade inflammation within adipose tissue. Obes Rev. 2018;19:686–97.CrossRef
32.
go back to reference Zhou Y, Yu X, Chen H, Sjöberg S, Roux J, Zhang L, et al. Leptin deficiency shifts mast cells toward anti-inflammatory actions and protects mice from obesity and diabetes by polarizing M2 macrophages. Cell Metab. 2015;22:1045–58.CrossRef Zhou Y, Yu X, Chen H, Sjöberg S, Roux J, Zhang L, et al. Leptin deficiency shifts mast cells toward anti-inflammatory actions and protects mice from obesity and diabetes by polarizing M2 macrophages. Cell Metab. 2015;22:1045–58.CrossRef
Metadata
Title
Leptin receptor is expressed by tissue mast cells
Authors
Paulina Żelechowska
Magdalena Wiktorska
Sylwia Różalska
Olga Stasikowska-Kanicka
Małgorzata Wągrowska-Danilewicz
Justyna Agier
Ewa Brzezińska-Błaszczyk
Publication date
01-10-2018
Publisher
Springer US
Published in
Immunologic Research / Issue 5/2018
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-018-9029-0

Other articles of this Issue 5/2018

Immunologic Research 5/2018 Go to the issue