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Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps - 24/12/11

Doi : 10.1016/j.jaci.2011.08.021 
Sarah Peterson, MD a, Julie A. Poposki, MS a, Deepti R. Nagarkar, PhD a, Regina T. Chustz, BS a, Anju T. Peters, MD a, Lydia A. Suh, BS a, Roderick Carter, BS a, James Norton, MS a, Kathleen E. Harris, BS a, Leslie C. Grammer, MD a, Bruce K. Tan, MD b, Rakesh K. Chandra, MD b, David B. Conley, MD b, Robert C. Kern, MD b, Robert P. Schleimer, PhD a, Atsushi Kato, PhD a,
a Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill 
b Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill 

Corresponding author: Atsushi Kato, PhD, Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, 240 E Huron, Chicago, IL 60611.

Abstract

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with TH2-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 TH2-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.

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Key words : Chronic rhinosinusitis, nasal polyps, Samter’s triad, CCL18, pulmonary and activation-regulated chemokine, M2 macrophages, mast cells

Abbreviations used : CCL18, CLC, CRS, CRSsNP, CRSwNP, DC, ECP, HPF, IMDM, MMR, NMFF, NP, PIC, STAB1, UT


Plan


 Supported in part by National Institutes of Health grants R01 HL078860, R01 AI072570, and R37 HL068546 and by a grant from the Ernest S. Bazley Trust.
 Disclosure of potential conflict of interest: R. C. Kern receives research support from the National Institutes of Health. R. P. Schleimer has consultant arrangements with ChemoCentryx and receives research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.


© 2011  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 129 - N° 1

P. 119 - janvier 2012 Retour au numéro
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