Skip to main content
SpringerLink
Log in

Expression of CysLTR1 and 2 in Maturating Lymphocytes of Hyperplasic Tonsils Compared to Peripheral Cells in Children

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Cysteinyl-leukotriene receptors 1 and 2 (CysLTR1 and 2) are related to allergic inflammatory responses. Recent studies demonstrated their role in lymphocyte division and maturation in the bone marrow. Few data are available about CysLTRs function in lymphocyte maturation in tonsils. The objectives of this study are to compare CysLTRs expression in peripheral blood lymphocytes with expression in maturating lymphocytes of hyperplasic tonsil and to check the influence of respiratory allergies in this process. Leukocytes of peripheral blood (PL) and hyperplasic tonsils of children were immunostained for CysLTR1, CysLTR2, CD3 (T cells), and CD19 (B cells) and read in flow cytometer. Lymphocyte of tonsils were divided in differentiating small cells (SC) and mitotic large cells (LC); percentage of B and T cells expressing CysLTRs was determined, and comparison was done using ANOVA and Tukey’s tests. Data were analyzed as a whole and categorizing patients according the presence of allergies. Sixty children were enrolled in this study. There was a large expression of CysLTR1 and 2 in CD3+ LC, and such expression decreased progressively in SC and PL. In B cells, the highest expression of CysLTR1 and 2 was found in PL while SC showed the lowest and LC showed the intermediate expression. This pattern kept unchanged in groups of allergic and non-allergic individuals. CysLTRs seem to be involved in lymphocyte maturation that occurs in tonsils, without influence of allergies. New studies aiming the clinic treatment of tonsil hyperplasia must be targeted to the development of drugs capable of blocking both CysLTR1 and 2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Noussios, G., J. Xanthopoulos, T. Zaraboukas, V. Vital, and I. Konstantinidis. 2003. Morphological study of development and functional activity of palatine tonsils in embryonic age. Acta Otorhinolaryngologica Italica 23(2): 98–101.

    CAS  PubMed  Google Scholar 

  2. Carter, K.A., N.E. Hathaway, and C.F. Lettieri. 2014. Common sleep disorders in children. American Family Physician 89(5): 368–77.

    PubMed  Google Scholar 

  3. Dell’Aringa, A.R., A.J. Juares, Cd Melo, J.C. Nardi, K. Kobari, and R.M. Perches Filho. 2005. Histological analysis of tonsillectomy and adenoidectomy specimens—January 2001 to May 2003. Brazilian Journal of Otorhinolaryngology 71(1): 18–22.

    Article  PubMed  Google Scholar 

  4. Rademakers, L.H. 1992. Dark and light zones of germinal centres of the human tonsil: an ultrastructural study with emphasis on heterogeneity of follicular dendritic cells. Cell and Tissue Research 269(2): 359–68.

    Article  CAS  PubMed  Google Scholar 

  5. Dayyat, E., L.D. Serpero, L. Kheirandish-Gozal, J.L. Goldman, A. Snow, and R. Bhattacharjee. 2009. Leukotriene pathways and in vitro adenotonsillar cell proliferation in children with obstructive sleep apnea. Chest 135: 1142–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McNeil, H.P., Adachi, R., and Stevens, R.L. 2007. Mast cell restricted tryptases: structure and function in inflammation and pathogen defense. The Journal of Biological Chemistry. 282:(29).

  7. Nathan, R.A. 2008. The pathophysiology, clinical impact, and management of nasal congestion in allergic rhinitis. Clinical Therapeutics 30(4): 573–86.

    Article  CAS  PubMed  Google Scholar 

  8. Denzlinger, C., L. Kanz, R. Möhle, and F. Bautz. 2001. Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Blood 97(11): 3433–40.

    Article  PubMed  Google Scholar 

  9. Lamoureux, J., J. Stankova, and M. Rola-Pleszczynski. 2006. Leukotriene D4 enhances immunoglobulin production in CD40-activated human B lymphocytes. The Journal of Allergy and Clinical Immunology 117(4): 924–30.

    Article  CAS  PubMed  Google Scholar 

  10. Chervin, R.D., K. Hedger, J.E. Dillon, and K.J. Pituch. 2000. Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Medicine 1(1): 21–32.

    Article  PubMed  Google Scholar 

  11. Certal, V., F.F. de Lima, J.C. Winck, I. Azevedo, and A. Costa-Pereira. 2015. Translation and cross-cultural adaptation of the pediatric sleep questionnaire into Portuguese language. International Journal of Pediatric Otorhinolaryngology 79(2): 175–8.

    Article  PubMed  Google Scholar 

  12. Brodsky, L. 1989. Modern assessment of tonsils and adenoids. Pediatric Clinics of North America 36(6): 1551–69.

    CAS  PubMed  Google Scholar 

  13. Caylakli, F., E. Hizal, I. Yilmaz, and C. Yilmazer. 2009. Correlation between adenoid-nasophatinx ratio and endoscopic examination of adenoid-hypertrophy: a blind, prospective clinical study. International Journal of Pediatric Otorhinolaryngology 73(11): 1532–5.

    Article  PubMed  Google Scholar 

  14. Lertsburapa, K., J.W. Schroeder Jr., and C. Sullivan. 2010. Assessment of adenoid size: a comparison of lateral radiographic measurements, radiologist assessment, and nasal endoscopy. International Journal of Pediatric Otorhinolaryngology 74(11): 1281–5.

    Article  PubMed  Google Scholar 

  15. Marshall, T. 1998. A review of tonsillectomy for recurrent throat infection. The British Journal of General Practice 48(431): 1331–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Cole, T.J., M.C. Bellizzi, K.M. Flegal, and W.H. Dietz. 2000. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320: 1240–1243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barlow, S.E., and the Expert Committee. 2007. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 120: S164–S192.

    Article  PubMed  Google Scholar 

  18. Kjeldsen, M.K., M. Perez-Andres, A. Schmitz, P. Johansen, M. Boegsted, M. Nyegaard, M. Gaihede, A. Bukh, H.E. Johnsen, A. Orfao, and K. Dybkaer. 2011. Multiparametric flow cytometry for identification and fluorescence activated cell sorting of five distinct B-cell subpopulations in normal tonsil tissue. American Journal of Clinical Pathology 136(6): 960–9. doi:10.1309/AJCPDQNP2U5DZHVV.

    Article  PubMed  Google Scholar 

  19. Marcus, C.L., L.J. Brooks, K.A. Draper, D. Gozal, A.C. Halbower, J. Jones, M.S. Schechter, S.D. Ward, S.H. Sheldon, R.N. Shiffman, C. Lehmann, K. Spruyt, and American Academy of Pediatrics. 2012. Diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics 130(3): e714–55.

    Article  PubMed  Google Scholar 

  20. Kotagal, S., C.D. Nichols, M.M. Grigg-Damberger, C.L. Marcus, M.B. Witmans, V.G. Kirk, L.A. D’Andrea, and T.F. Hoban. 2012. Non-respiratory indications for polysomnography and related procedures in children: an evidence-based review. Sleep 35(11): 1451–66. doi:10.5665/sleep.2188.

    PubMed  PubMed Central  Google Scholar 

  21. Tsaoussoglou, M., Lianou Loukia, Maragozidis Panagiotis, Hatzinikolaou Souzana, Mavromati Maria, Orologas Nikolaos, Panaghiotopoulou-Gartagani Polytimi, Rassidakis George, A. Nikolaos, A. Balatsos, Chrousos George, and G. Athanasios. 2012. Kaditis: cysteinyl leukotriene receptors in tonsillar B- and T-lymphocytes from children with obstructive sleep apnea. Sleep Medicine 13: 879–85.

    Article  PubMed  Google Scholar 

  22. Hsu, S.M., and E.S. Jaffe. 1985. Phenotypic expression of T lymphocytes in thymus and peripheral lymphoid tissues. The American Journal of Pathology 121(1): 69–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Wipfler, D., G.V. Srinivasan, H. Sadick, B. Kniep, S. Arming, M. Willhauck-Fleckenstein, R. Vlasak, R. Schauer, and R. Schwartz-Albiez. 2011. Differentially regulated expression of 9-O-acetyl GD3 (CD60b) and 7-O-acetyl-GD3 (CD60c) during differentiation and maturation of human T and B lymphocytes. Glycobiology 21(9): 1161–72.

    Article  CAS  PubMed  Google Scholar 

  24. Kaditis, A.G., M.G. Ioannou, K. Chaidas, E.I. Alexopoulos, M. Apostolidou, T. Apostolidis, G. Koukoulis, and K. Gourgoulianis. 2008. Cysteinyl leukotriene receptors are expressed by tonsillar T cells of children with obstructive sleep apnea. Chest 134(2): 324–31.

    Article  PubMed  Google Scholar 

  25. Shen, Y., Z. Xu, Z. Huang, J. Xu, Q. Qin, and K. Shen. 2012. Increased cysteinyl leukotriene concentration and receptor expression in tonsillar tissues of Chinese children with sleep-disordered breathing. International Immunopharmacology 13(4): 371–6.

    Article  CAS  PubMed  Google Scholar 

  26. Tsaoussoglou, M., S. Hatzinikolaou, G.E. Baltatzis, L. Lianou, P. Maragozidis, N.A. Balatsos, G. Chrousos, and A.G. Kaditis. 2014. Expression of leukotriene biosynthetic enzymes in tonsillar tissue of children with obstructive sleep apnea: a prospective nonrandomized study. JAMA Otolaryngology - Head & Neck Surgery 140(10): 944–50. doi:10.1001/jamaoto.2014.1936.

    Article  Google Scholar 

  27. Mahshid, Y., M.R. Lisy, X. Wang, R. Spanbroek, J. Flygare, B. Christensson, M. Björkholm, B. Sander, A.J. Habenicht, and H.E. Claesson. 2009. High expression of 5-lipoxygenase in normal and malignant mantle zone B lymphocytes. BMC Immunology 10: 2.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lynch, K.R., P. Gary, G.P. O’neill, Q. Qingyun Liu, D.-S. Im, N. Sawyer, K.M. Metters, N. Coulombe, M. Abramovitz, D.J. Figueroa, Z. Zeng, B.M. Connolly, C. Bai, C.P. Austin, A. Chateauneuf, R. Stocco, G.M. Greig, S. Kargman, S.B. Hooks, E. Hosfield, D.L. Jr Williams, A.W. Ford-Hutchinson, C.T. Caskey, and J.F. Evans. 1999. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 399: 789–793.

    Article  CAS  PubMed  Google Scholar 

  29. Parmentier, C.N., E. Fuerst, J. McDonald, H. Bowen, T.H. Lee, J.E. Pease, G. Woszczek, and D.J. Cousins. 2012. Human T(H)2 cells respond to cysteinyl leukotrienes through selective expression of cysteinyl leukotriene receptor 1. The Journal of Allergy and Clinical Immunology 129(4): 1136–42. doi:10.1016/j.jaci.2012.01.057.

    Article  CAS  PubMed  Google Scholar 

  30. Sarau, H.M., R.S. Ames, J. Chambers, C. Ellis, N. Elshourbagy, J.J. Foley, D.B. Schmidt, R.M. Muccitelli, O. Jenkins, P.R. Murdock, N.C. Herrity, W. Halsey, G. Sathe, A.I. Muir, P. Nuthulaganti, G.M. Dytko, P.T. Buckley, S. Wilson, D.J. Bergsma, and D.W. Hay. 1999. Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Molecular Pharmaceutics 56(3): 657–663.

    CAS  Google Scholar 

  31. Takasaki, J., M. Kamohara, M. Matsumoto, T. Saito, T. Sugimoto, T. Ohishi, H. Ishii, T. Ota, T. Nishikawa, Y. Kawai, Y. Masuho, T. Isogai, Y. Suzuki, S. Sugano, and K. Furuichi. 2000. The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. Biochemical and Biophysical Research Communications 274(2): 316–322.

    Article  CAS  PubMed  Google Scholar 

  32. Heise, C.E., B.F. O’Dowd, D.J. Figueroa, N. Sawyer, T. Nguyen, D.-S. Im, R. Stocco, J.N. Bellefeuille, M. Abramovitz, R. Cheng, D.L. Williams Jr., Z. Zeng, Q. Liu, L. Ma, M.K. Clements, N. Coulombe, Y. Liu, C.P. Austin, S.R. George, G.P. O’Neill, K.M. Metters, K.R. Lynch, and J.F. Evans. 2000. Characterization of the human cysteinyl leukotriene 2 receptor. The Journal of Biological Chemistry 275(39): 30531–30536.

    Article  CAS  PubMed  Google Scholar 

  33. Mita, H., M. Hasegawa, H. Saito, and K. Akiyama. 2001. Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils. Clinical and Experimental Allergy 31(11): 1714–1723.

    Article  CAS  PubMed  Google Scholar 

  34. van den Akker, E.H., E.A. Sanders, B.K. van Staaij, G.T. Rijkers, M.M. Rovers, A.W. Hoes, and A.G. Schilder. 2006. Long-term effects of pediatric adenotonsillectomy on serum immunoglobulin levels: results of a randomized controlled trial. Annals of Allergy, Asthma & Immunology 97(2): 251–6.

    Article  Google Scholar 

  35. Sadeghi-Shabestari, M., Y. Jabbari Moghaddam, and H. Ghaharri. 2011. Is there any correlation between allergy and adenotonsillar tissue hypertrophy? International Journal of Pediatric Otorhinolaryngology 75(4): 589–91.

    Article  CAS  PubMed  Google Scholar 

  36. Nadal, D., N. Soh, E. Schläpfer, J.M. Bernstein, and P.L. Ogra. 1992. Distribution characteristics of immunoglobulin-secreting cells in adenoids. Relationship to age and disease. International Journal of Pediatric Otorhinolaryngology 24(2): 121–30.

    Article  CAS  PubMed  Google Scholar 

  37. Salvi, S., and S.T. Holgate. 1999. Could the airway epithelium play an important role in mucosal immunoglobulin A production? Clinical and Experimental Allergy 29(12): 1597–605.

    Article  CAS  PubMed  Google Scholar 

  38. Sousa, C.A., C.L. César, M.B. Barros, L. Carandina, M. Goldbaum, and J.C. Pereira. 2012. Respiratory diseases and associated factors: population-based study in São Paulo, 2008-2009. Revista de Saúde Pública 46(1): 16–25.

    Article  PubMed  Google Scholar 

  39. Nicolussi, F.H., A.P. Santos, S.C. André, T.B. Veiga, and A.M. Takayanagui. 2014. Air pollution and respiratory allergic diseases in schoolchildren. Revista de Saúde Pública 48(2): 326–30.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Peters-Golden, M., M.M. Gleason, and A. Togias. 2006. Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis. Clinical and Experimental Allergy 36(6): 689–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mewes, T., H. Riechelmann, and L. Klimek. 1996. Increased in vitro cysteinyl leukotriene release from blood leukocytes in patients with asthma, nasal polyps, and aspirin intolerance. Allergy 51(7): 506–10.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otolaryngology of Clinics Hospital, University of Sao Paulo—Brazil, Av. Dr. Eneas de Carvalho Aguiar, 255 - 6° andar - sala 6167, 05403-000, Sao Paulo, SP, Brazil

    Bruno Peres Paulucci & Renata Cantisani di Francesco

  2. Department of Hematology of Clinics Hospital, University of Sao Paulo—Brazil, Sao Paulo, SP, Brazil

    Juliana Pereira

  3. Department of Pathology of Clinics Hospital, University of Sao Paulo—Brazil, Sao Paulo, SP, Brazil

    Patricia Picciarelli

  4. Laboratory of Research in Hematology of Clinics Hospital, University of Sao Paulo—Brazil, Sao Paulo, SP, Brazil

    Debora Levy

Authors
  1. Bruno Peres Paulucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juliana Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patricia Picciarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Debora Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Renata Cantisani di Francesco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruno Peres Paulucci.

Ethics declarations

Funding

The authors thank the Research Support Foundation of São Paulo State (FAPESP) for financial subsidy and technical support—grant number 2013/19500-3.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paulucci, B.P., Pereira, J., Picciarelli, P. et al. Expression of CysLTR1 and 2 in Maturating Lymphocytes of Hyperplasic Tonsils Compared to Peripheral Cells in Children. Inflammation 39, 1216–1224 (2016). https://doi.org/10.1007/s10753-016-0357-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-016-0357-8

KEY WORDS

Search

Navigation