Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps

J Allergy Clin Immunol. 2012 Jan;129(1):119-27.e1-9. doi: 10.1016/j.jaci.2011.08.021. Epub 2011 Sep 23.


Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with T(H)2-dominant inflammation, including eosinophilia, which is in contrast to chronic rhinosinusitis (CRS) without nasal polyps (NPs). CC chemokine ligand 18 (CCL18)/pulmonary and activation-regulated chemokine is known to recruit naive T cells, B cells, and immature dendritic cells, as well as to activate fibroblasts. CCL18 is thought to be involved in T(H)2-related inflammatory diseases, including asthma and atopic dermatitis.

Objective: The objective of this study was to investigate the expression of CCL18 in patients with CRS.

Methods: Using NP tissue and uncinate tissue (UT) from control subjects and patients with CRS, we examined the expression of CCL18 mRNA using real-time PCR and measured CCL18 protein using ELISA, Western blotting, and immunofluorescence.

Results: Compared with UT tissue from control subjects, CCL18 mRNA levels were significantly increased in NPs (P < .001) and UT (P < .05) from patients with CRSwNP but not in UT from patients with CRS without NPs. Similarly, CCL18 protein levels were increased in NPs and UT from patients with CRSwNP, and levels were even higher in patients with Samter's triad. Immunohistochemical analysis revealed CCL18 expression in inflammatory cells, and CCL18(+) cell numbers were significantly increased in NPs. Immunofluorescence data showed colocalization of CCL18 in CD68(+)/CD163(+)/macrophage mannose receptor-positive M2 macrophages and tryptase-positive mast cells in NPs. Levels of CCL18 correlated with markers of M2 macrophages but not with tryptase levels, suggesting that M2 macrophages are major CCL18-producing cells in NPs.

Conclusion: Overproduction of CCL18 might contribute to the pathogenesis of CRSwNP through its known activities, which include recruitment of lymphocytes and dendritic cells, activation of fibroblasts, and initiation of local inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Line
  • Cells, Cultured
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism*
  • Chronic Disease
  • Female
  • Humans
  • Macrophages / immunology
  • Male
  • Middle Aged
  • Nasal Mucosa / immunology
  • Nasal Polyps / complications*
  • Nasal Polyps / genetics
  • Rhinitis / complications
  • Rhinitis / genetics
  • Rhinitis / immunology*
  • Sinusitis / complications
  • Sinusitis / genetics
  • Sinusitis / immunology*
  • Young Adult


  • CCL18 protein, human
  • Chemokines, CC