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Increased expression of chemokine receptors CCR1 and CCR3 in nasal polyps: molecular basis for recruitment of the granulocyte infiltrate

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Abstract

Inflammatory processes play an important role in the development of nasal polyps (NP), but the etiology and, to a high degree also, the pathogenesis of NP are not fully understood. The role of several cytokines and chemokines such as eotaxins, IL-4, IL-5, IL-6, IL-8, and RANTES has been reported in NP. Herewith, we investigated the expression and pattern of distribution of chemokine receptors CCR1 and CCR3 in nasal polyps. Immunohistochemical detection was carried out in frozen sections of biopsies from 22 NP and 18 nasal mucosa specimens in both the epithelial and stromal compartments. Fluorescence microscopy and computerized image analysis revealed a statistically significant increased number of CCR1 (45.2 ± 2.8 vs. 15.1 ± 1.9, p < 0.001)-positive as well as CCR3 (16.4 ± 1.4 vs. 9.7 ± 1.1, p < 0.001)-positive cells in the stroma of NP compared to nasal mucosa. In comparison to healthy nasal mucosa, increased positivity of CCR3 was detected in the epithelial compartment of NP. Our data suggest that increased expression of CCR1 and CCR3 chemokine receptors may, in accord with various chemokines, contribute to the pathogenesis of nasal polyposis by facilitating increased migration and prolonged accumulation of inflammatory cells, e.g., eosinophils, in the inflammatory infiltrate of NP.

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Abbreviations

CCL:

C-C chemokine ligands

CCR1:

C-C chemokine receptor type 1

CCR3:

C-C chemokine receptor type 3

CD:

Cluster of differentiation

CY3:

Indocarbocyanine

GM-CSF:

Granulocyte/macrophage colony-stimulating factor

H&E:

Hematoxylin & eosin

ICAM-1:

Intercellular adhesion molecule 1

IgG:

Immunoglobulin G

IL:

Interleukin

MCP-3:

Monocyte chemoattractant protein 3

MCP-4:

Monocyte chemoattractant protein 4

MEC:

Mucosae-associated epithelial chemokine

MIP-1 α:

Macrophage inflammatory protein 1α

MIP-3:

Macrophage inflammatory protein-3

NFκ-B:

Nuclear factor-kappaB

NM:

Nasal mucosa

NP:

Nasal polyps

RANTES:

Regulated on activation, normal T expressed and secreted protein

TBS:

Tris-buffered saline

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

VCAM-1:

Vascular cell adhesion molecule 1

References

  • Allen JS, Eisma R, LaFreniere D et al (1998) Characterization of the eosinophil chemokine RANTES in nasal polyps. Ann Otol Rhinol Laryngol 107:416–420

    PubMed  CAS  Google Scholar 

  • Bachert C, Wagenmann M, Hauser U et al (1997) IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol 99:837–842

    Article  PubMed  CAS  Google Scholar 

  • Bachert C, Gevaert P, Holtappels G et al (2002) Mediators in nasal polyposis. Curr Allergy Asthma Rep 2:481–487

    Article  PubMed  Google Scholar 

  • Bachert C, Hörmann K, Mösges R et al (2003) An update on the diagnosis and treatment of sinusitis and nasal polyposis. Allergy 58:176–191

    Article  PubMed  CAS  Google Scholar 

  • Berahovich RD, Miao Z, Wang Y et al (2005) Proteolytic activation of alternative CCR1 ligands in inflammation. J Immunol 174:7341–7351

    PubMed  CAS  Google Scholar 

  • Bernstein JM, Ballow M, Rich G et al (2004) Lymphocyte subpopulations and cytokines in nasal polyps: is there a local immune system in the nasal polyp? Otolaryngol Head Neck Surg 130:526–535

    Article  PubMed  Google Scholar 

  • Daugherty BL, Siciliano SJ, DeMartino JA et al (1996) Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med 183:2349–2354

    Article  PubMed  CAS  Google Scholar 

  • Fokkens W, Lund V, Mullol J (2005) European position paper on rhinosinusitis and nasal polyps. Rhinology Suppl 18:1–87

    Google Scholar 

  • Funda DP, Tucková L, Farré MA et al (2001) CD14 is expressed and released as soluble CD14 by human intestinal epithelial cells in vitro: lipopolysaccharide activation of epithelial cells revisited. Infect Immun 69:3772–3781

    Article  PubMed  CAS  Google Scholar 

  • Fundová P, Filipovský T, Funda DP et al (2008) Expression of IGF-1R and iNOS in nasal polyps; epithelial cell homeostasis and innate immune mechanisms in pathogenesis of nasal polyposis. Folia Microbiol (Praha) 53:558–562

    Article  Google Scholar 

  • Furuichi K, Gao JL, Horuk R et al (2008) Chemokine receptor CCR1 regulates inflammatory cell infiltration after renal ischemia–reperfusion injury. J Immunol 181:8670–8676

    PubMed  CAS  Google Scholar 

  • Gao JL, Kuhns DB, Tiffany HL et al (1993) Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor. J Exp Med 177:1421–1427

    Article  PubMed  CAS  Google Scholar 

  • Hwang J, Son KN, Kim CW et al (2005) Human CC chemokine CCL23, a ligand for CCR1, induces endothelial cell migration and promotes angiogenesis. Cytokine 30:254–263

    Article  PubMed  CAS  Google Scholar 

  • Kitayama J, Mackay CR, Ponath PD et al (1998) The C-C chemokine receptor CCR3 participates in stimulation of eosinophil arrest on inflammatory endothelium in shear flow. J Clin Invest 101:2017–2024

    Article  PubMed  CAS  Google Scholar 

  • Laing KJ, Secombes CJ (2004) Chemokines. Dev Comp Immunol 28:443–460

    Article  PubMed  CAS  Google Scholar 

  • Lin CF, Tsai CH, Cheng CH et al (2007) Expression of Toll-like receptors in cultured nasal epithelial cells. Acta Otolaryngol 127:395–402

    Article  PubMed  CAS  Google Scholar 

  • Meyer JE, Bartels J, Görögh T et al (2005) The role of RANTES in nasal polyposis. Am J Rhinol 19:15–20

    PubMed  Google Scholar 

  • Murphy PM (2002) International union of pharmacology. XXX. Update on chemokine receptor nomenclature. Pharmacol Rev 54:227–229

    Article  PubMed  CAS  Google Scholar 

  • Neote K, DiGregorio D, Mak JY et al (1993) Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell 72:415–425

    Article  PubMed  CAS  Google Scholar 

  • Nonaka M, Pawankar R, Saji F et al (1999) Distinct expression of RANTES and GM-CSF by lipopolysaccharide in human nasal fibroblasts but not in other airway fibroblasts. Int Arch Allergy Immunol 119:314–321

    Article  PubMed  CAS  Google Scholar 

  • Pawankar R (2003) Nasal polyposis: an update. Curr Opin Allergy Clin Immunol 3:1–6

    Article  PubMed  CAS  Google Scholar 

  • Ponath PD, Qin S, Ringler DJ et al (1996) Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest 97:604–612

    Article  PubMed  CAS  Google Scholar 

  • Poposki JA, Uzzaman A, Nagarkar DR et al (2011) Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 128:73–81

    Article  PubMed  CAS  Google Scholar 

  • Roca-Ferrer J, Mullol J, Lopez E et al (1997) Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion. Eur Respir J 10:1489–1495

    Article  PubMed  CAS  Google Scholar 

  • Sallusto F, Mackay CR, Lanzavecchia A (1997) Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277:2005–2007

    Article  PubMed  CAS  Google Scholar 

  • Sánchez-Segura A, Brieva JA, Rodríguez C (1998) T lymphocytes that infiltrate nasal polyps have a specialized phenotype and produce a mixed TH1/TH2 pattern of cytokines. J Allergy Clin Immunol 102:953–960

    Article  PubMed  Google Scholar 

  • Shin SH, Lee SH, Jeong HS et al (2003) The effect of nasal polyp epithelial cells on eosinophil activation. Laryngoscope 113:1374–1377

    Article  PubMed  Google Scholar 

  • Simon HU, Yousefi S, Schranz C et al (1997) Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia. J Immunol 158:3902–3908

    PubMed  CAS  Google Scholar 

  • Stadnyk AW (2002) Intestinal epithelial cells as a source of inflammatory cytokines and chemokines. Can J Gastroenterol 16:241–246

    PubMed  Google Scholar 

  • Stoop AE, van der Heijden HA, Biewenga J et al (1993) Eosinophils in nasal polyps and nasal mucosa: an immunohistochemical study. J Allergy Clin Immunol 91:616–622

    Article  PubMed  CAS  Google Scholar 

  • Symon FA, McNulty CA, Wardlaw AJ (1999) P- and L-selectin mediate binding of T cells to chronically inflamed human airway endothelium. Eur J Immunol 29:1324–1333

    Article  PubMed  CAS  Google Scholar 

  • Tingsgaard PK, Larsen PL, Bock T et al (1998) Expression of intercellular adhesion molecule-1 on the vascular endothelium in nasal polyps before, during and after topical glucocorticoid treatment. Acta Otolaryngol 118:404–408

    Article  PubMed  CAS  Google Scholar 

  • Tingsgaard PK, Bock T, Larsen PL et al (1999) Topical budesonide treatment reduces endothelial expression of intercellular adhesion molecules (vascular cell adhesion molecule-1 and P-selectin) and eosinophil infiltration in nasal polyps. Acta Otolaryngol 119:362–368

    Article  PubMed  CAS  Google Scholar 

  • Tlaskalová-Hogenová H, Stĕpánková R, Tucková L et al (1998) Autoimmunity, immunodeficiency and mucosal infections: chronic intestinal inflammation as a sensitive indicator of immunoregulatory defects in response to normal luminal microflora. Folia Microbiol (Praha) 43:545–550

    Article  Google Scholar 

  • Wang HB, Ghiran I, Matthaei K et al (2007a) Airway eosinophils: allergic inflammation recruited professional antigen-presenting cells. J Immunol 179:7585–7592

    PubMed  CAS  Google Scholar 

  • Wang J, Matsukura S, Watanabe S et al (2007b) Involvement of Toll-like receptors in the immune response of nasal polyp epithelial cells. Clin Immunol 124:345–352

    Article  PubMed  CAS  Google Scholar 

  • Xaubet A, Mullol J, López E et al (1994) Comparison of the role of nasal polyp and normal nasal mucosal epithelial cells on in vitro eosinophil survival. Mediation by GM-CSF and inhibition by dexamethasone. Clin Exp Allergy 24:307–317

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the grant IGA MZ NS10054 from the Grant Agency of the Ministry of Health of the Czech Republic.

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Correspondence to P. Fundová.

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Fundová, P., Funda, D.P., Kovář, D. et al. Increased expression of chemokine receptors CCR1 and CCR3 in nasal polyps: molecular basis for recruitment of the granulocyte infiltrate. Folia Microbiol 58, 219–224 (2013). https://doi.org/10.1007/s12223-012-0194-6

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  • DOI: https://doi.org/10.1007/s12223-012-0194-6

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