Top

Published in:

01-08-2016 | ORIGINAL ARTICLE

Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen

Authors: Rangel L. Silva, Fernanda V. Castanheira, Jozi G. Figueiredo, Gabriel S. Bassi, Sérgio H. Ferreira, Fernando Q. Cunha, Thiago M. Cunha, Alexandre Kanashiro

Published in: Inflammation | Issue 4/2016

Abstract

The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta-adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor.

Medzhitov, R. 2008. Origin and physiological roles of inflammation. Nature 454: 428–35.CrossRefPubMed

Kolaczkowska, E., and P. Kubes. 2013. Neutrophil recruitment and function in health and inflammation. Nature Reviews. Immunology 13(3): 159–75.CrossRefPubMed

McDonald, B., K. Pittman, G.B. Menezes, S.A. Hirota, I. Slaba, C.C. Waterhouse, P.L. Beck, D.A. Muruve, and P. Kubes. 2010. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330(6002): 362–6.CrossRefPubMed

Alves-Filho, J.C., A. Freitas, F. Spiller, F.O. Souto, and F.Q. Cunha. 2008. The role of neutrophils in severe sepsis. Shock 30: 3–9.CrossRefPubMed

Sherwood, E.R., and T. Toliver-Kinsky. 2004. Mechanisms of the inflammatory response. Best Practice & Research Clinical Anaesthesiology 18: 385–405.CrossRef

Segel, G.B., M.W. Halterman, and M.A. Lichtman. 2011. The paradox of the neutrophil’s role in tissue injury. Journal of Leukocyte Biology 89(3): 359–7.CrossRefPubMed

Németh, T., and A. Mócsai. 2012. The role of neutrophils in autoimmune diseases. Immunology Letters 143: 9–19.CrossRefPubMed

Mackay, C.R. 2008. Moving targets: cell migration inhibitors as new anti-inflammatory therapies. Nature Immunology 9: 988–98.CrossRefPubMed

Sun, J., V. Singh, R. Kajino-Sakamoto, and A. Aballay. 2011. Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 332: 729–32.CrossRefPubMedPubMedCentral

10.

Torres-Rosas, R., G. Yehia, G. Peña, P. Mishra, Thompson-Bonilla M. del Rocio, M.A. Moreno-Eutimio, L.A. Arriaga-Pizano, A. Isibasi, and L. Ulloa. 2014. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nature Medicine 20(3): 291–5.CrossRefPubMedPubMedCentral

11.

Ulloa, L. 2005. The vagus nerve and the nicotinic anti-inflammatory pathway. Nature Reviews. Drug Discovery 4(8): 673–84.CrossRefPubMed

12.

Vida, G., G. Peña, E.A. Deitch, and L. Ulloa. 2011. α7-Cholinergic receptor mediates vagal induction of splenic norepinephrine. Journal Immunology 186(7): 4340–6.CrossRef

13.

Tracey, K.J. 2011. Physiology and immunology of the cholinergic anti-inflammatory pathway. Journal of Clinical Investigation 117: 289–96.CrossRef

14.

Borovikova, L.V., S. Ivanova, M. Zhang, H. Yang, G.I. Botchkina, L.R. Watkins, H. Wang, N. Abumrad, J.W. Eaton, and K.J. Tracey. 2000. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785): 458–62.CrossRefPubMed

15.

Rosas-Ballina, M., M. Ochani, W.R. Parrish, K. Ochani, Y.T. Harris, J.M. Huston, S. Chavan, and K.J. Tracey. 2008. Splenic nerve is required for cholinergic anti-inflammatory pathway control of TNF in endotoxemia. Proceedings of the National Academy of Sciences 105: 11008–13.CrossRef

16.

Rosas-Ballina, M., P.S. Olofsson, M. Ochani, S.I. Valdés-Ferrer, Y.A. Levine, C. Reardon, M.W. Tusche, V.A. Pavlov, U. Andersson, S. Chavan, T.W. Mak, and K.J. Tracey. 2011. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334(6052): 98–101.CrossRefPubMedPubMedCentral

17.

Vida, G., G. Peña, A. Kanashiro, M.R. Thompson-Bonilla, D. Palange, E.A. Deitch, and L. Ulloa. 2011. β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system. FASEB Journal 25: 4476–85.CrossRefPubMedPubMedCentral

18.

Wang, H., M. Yu, M. Ochani, C.A. Amella, M. Tanovic, S. Susarla, J.H. Li, H. Wang, H. Yang, L. Ulloa, Y. Al-Abed, C.J. Czura, and K.J. Tracey. 2003. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421(6921): 384–8.CrossRefPubMed

19.

Saeed, R.W., S. Varma, T. Peng-Nemeroff, B. Sherry, D. Balakhaneh, J. Huston, K.J. Tracey, Y. Al-Abed, and C.N. Metz. 2005. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. The Journal of Experimental Medicine 201(7): 1113–23.CrossRefPubMedPubMedCentral

20.

Huston, J.M., M. Rosas-Ballina, X. Xue, O. Dowling, K. Ochani, M. Ochani, M.M. Yeboah, P.K. Chatterjee, K.J. Tracey, and C.N. Metz. 2009. Cholinergic neural signals to the spleen down-regulate leukocyte trafficking via CD11b. Journal of Immunology 183(1): 552–9.CrossRef

21.

Mabley, J., S. Gordon, and P. Pacher. 2011. Nicotine exerts an anti-inflammatory effect in a murine model of acute lung injury. Inflammation 34(4): 231–7.CrossRefPubMedPubMedCentral

22.

Tracey, K.J. 2010. Understanding immunity requires more than immunology. Nature Immunology 11: 561–564.CrossRefPubMedPubMedCentral

23.

Figueiredo, J., A.E. Ferreira, R.L. Silva, L. Ulloa, P. Grieco, T.M. Cunha, S.H. Ferreira, F.Q. Cunha, and A. Kanashiro. 2013. NDP-MSH inhibits neutrophil migration through nicotinic and adrenergic receptors in experimental peritonitis. Naunyn-Schmiedeberg’s Archives of Pharmacology 386(4): 311–8.CrossRefPubMed

24.

Elenkov, I.J., G. Haskó, K.J. Kovács, and E.S. Vizi. 1995. Modulation of lipopolysaccharide-induced tumor necrosis factor-alpha production by selective alpha- and beta-adrenergic drugs in mice. Journal of Neuroimmunology 61(2): 123–31.CrossRefPubMed

25.

Karimi, K., J. Bienenstock, L. Wang, and P. Forsythe. 2010. The vagus nerve modulates CD4+ T cell activity. Brain, Behavior, and Immunity 24(2): 316–23.CrossRefPubMed

26.

Huston, J.M., M. Ochani, M. Rosas-Ballina, H. Liao, K. Ochani, V.A. Pavlov, M. Gallowitsch-Puerta, M. Ashok, C.J. Czura, B. Foxwell, K.J. Tracey, and L. Ulloa. 2006. Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis. The Journal of Experimental Medicine 203(7): 1623–8.CrossRefPubMedPubMedCentral

27.

Rios-Santos, F., J.C. Alves-Filho, F.O. Souto, F. Spiller, A. Freitas, C.M.C. Lotufo, M.B.P. Soares, R.R. Santos, M.M. Teixeira, and F.Q. Cunha. 2007. Down-regulation of CXCR2 on neutrophils in severe sepsis is mediated by inducible nitric oxide synthase-derived nitric oxide. American Journal of Respiratory and Critical Care Medicine 175(5): 490–497.CrossRefPubMed

28.

Vieira, S.M., H.P. Lemos, R. Grespan, M.H. Napimoga, D. Dal-Secco, A. Freitas, T.M. Cunha, W.A. Verri Jr., D.A. Souza-Junior, M.C. Jamur, K.S. Fernandes, C. Oliver, J.S. Silva, M.M. Teixeira, and F.Q. Cunha. 2009. A crucial role for TNF-alpha in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5. British Journal of Pharmacology 158(3): 779–89.CrossRefPubMedPubMedCentral

29.

Dantzer, R., J.C. O’Connor, G.G. Freund, R.W. Johnson, and K.W. Kelley. 2008. From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience 9: 46–56.CrossRefPubMedPubMedCentral

30.

Steinman, L. 2004. Elaborate interactions between the immune and nervous systems. Nature Immunology 5: 575–81.CrossRefPubMed

31.

Imura, H., and J. Fukata. 1994. Endocrine-paracrine interaction in communication between the immune and endocrine systems. Activation of the hypothalamic-pituitary-adrenal axis in inflammation. European Journal of Endocrinology 130(1): 32–7.CrossRefPubMed

32.

Szelényi, J., J.P. Kiss, and E.S. Vizi. 2000. Differential involvement of sympathetic nervous system and immune system in the modulation of TNF-alpha production by alpha2- and beta-adrenoceptors in mice. Journal of Neuroimmunology 103(1): 34–40.CrossRefPubMed

33.

Spengler, R.N., S.W. Chensue, D.A. Giacherio, N. Blenk, and S.L. Kunkel. 1994. Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro. Journal of Immunology 152(6): 3024–31.

34.

Haskó, G., Z.H. Németh, C. Szabó, G. Zsilla, A.L. Salzman, and E.S. Vizi. 1998. Isoproterenol inhibits Il-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages. Brain Research Bulletin 45(2): 183–7.CrossRefPubMed

35.

Mert, T., B. Tugtag, M. Kilinc, E. Sahin, H. Oksuz, and Y. Gunes. 2014. Preventive and therapeutic effects of a beta adrenoreceptor agonist, dobutamine, in carrageenan-induced inflammatory nociception in rats. Inflammation 37(5): 1814–25.CrossRefPubMed

36.

Xiang, H., B. Hu, Z. Li, and J. Li. 2014. Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Inflammation 37(5): 1763–70.CrossRefPubMed

37.

Giuliani, D., A. Ottani, D. Altavilla, C. Bazzani, F. Squadrito, and S. Guarini. 2010. Melanocortins and the cholinergic anti-inflammatory pathway. Advances in Experimental Medicine and Biology 681: 71–87.CrossRefPubMed

38.

Bugajski, A.J., D. Zurowski, P. Thor, and A. Gadek-Michalska. 2007. Effect of subdiaphragmatic vagotomy and cholinergic agents in the hypothalamic-pituitary-adrenal axis activity. Journal of Physiology and Pharmacology 58(2): 335–47.PubMed

39.

Scanzano, A., L. Schembri, E. Rasini, A. Luini, J. Dallatorre, M. Legnaro, R. Bombelli, T. Congiu, M. Cosentino, and F. Marino. 2015. Adrenergic modulation of migration, CD11b and CD18 expression, ROS and interleukin-8 production by human polymorphonuclear leukocytes. Inflammation Research 64(2): 127–35.CrossRefPubMed

40.

Yu, H., Y.H. Yang, R. Rajaiah, and K.D. Moudgil. 2011. Nicotine-induced differential modulation of autoimmune arthritis in the Lewis rat involves changes in interleukin-17 and anti-cyclic citrullinated peptide antibodies. Arthritis and Rheumatology 63(4): 981–91.CrossRef

41.

Boland, C., V. Collet, E. Laterre, C. Lecuivre, X. Wittebole, and P.F. Laterre. 2011. Electrical vagus nerve stimulation and nicotine effects in peritonitis-induced acute lung injury in rats. Inflammation 34(1): 29–35.CrossRefPubMed

42.

Nabe, T., F. Hosokawa, K. Matsuya, T. Morishita, A. Ikedo, M. Fujii, N. Mizutani, S. Yoshino, and D.D. Chaplin. 2011. Important role of neutrophils in the late asthmatic response in mice. Life Science 88(25-26): 1127–35.CrossRef

43.

Blanchet, M.R., E. Israël-Assayag, and Y. Cormier. 2005. Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist. European Respiratory Journal 26(1): 21–7.CrossRefPubMed

44.

Rehani, K., D.A. Scott, D. Renaud, H. Hamza, L.R. Williams, H. Wang, and M. Martin. 2008. Cotinine-induced convergence of the cholinergic and PI3 kinase-dependent anti-inflammatory pathways in innate immune cells. Biochimica et Biophysica Acta 1783(3): 375–82.CrossRefPubMed

45.

Parrish, W.R., M. Rosas-Ballina, M. Gallowitsch-Puerta, M. Ochani, K. Ochani, L.H. Yang, L. Hudson, X. Lin, N. Patel, S.M. Johnson, S. Chavan, R.S. Goldstein, C.J. Czura, E.J. Miller, Y. Al-Abed, K.J. Tracey, and V.A. Pavlov. 2008. Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling. Molecular Medicine 14(9-10): 567–74.CrossRefPubMedPubMedCentral

Title: Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen
Authors: Rangel L. Silva
Fernanda V. Castanheira
Jozi G. Figueiredo
Gabriel S. Bassi
Sérgio H. Ferreira
Fernando Q. Cunha
Thiago M. Cunha
Alexandre Kanashiro
Publication date: 01-08-2016
Publisher: Springer US
Published in: Inflammation / Issue 4/2016
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-016-0372-9

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2016

Anti-inflammatory Evaluation and Toxicological Analysis of Campomanesia xanthocarpa Berg

Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell

A Recombinant DNA Plasmid Encoding the sIL-4R-NAP Fusion Protein Suppress Airway Inflammation in an OVA-Induced Mouse Model of Asthma

Optimization of Folate-Targeted Immunotherapy for the Treatment of Experimental Arthritis

Infiltration of IL-17-Producing T Cells and Treg Cells in a Mouse Model of Smoke-Induced Emphysema

Inhibiting High-Mobility Group Box 1 (HMGB1) Attenuates Inflammatory Cytokine Expression and Neurological Deficit in Ischemic Brain Injury Following Cardiac Arrest in Rats

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page